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Brancoli, Daniel Luz 1986. "O efeito da ivermectina na duração das fases de decomposição, sobre os insetos necrófagos e interpretação termográfica da distribuição espacial da massa larval de dípteros em carcaças de cabras (Capra aegragrus hircus L.,1758)." [s.n.], 2013. http://repositorio.unicamp.br/jspui/handle/REPOSIP/317460.
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Orientador: Arício Xavier LinharesDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia
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Resumo: A estimativa do intervalo pós-morte (IPM), período entre a ocorrência da morte e o momento em que o corpo ou carcaça é encontrado, é uma das principais utilizações de insetos na área forense. A partir de informações sobre a biologia, ecologia e distribuição geográfica dos insetos, bem como do comportamento de toda fauna presente em um corpo é possível estimar o menor intervalo da ocorrência da morte. Diversos fatores tais como temperatura, umidade, presença de substâncias tóxicas nos tecidos de uma carcaça, podem interferir no ciclo de vida de um inseto, afetando diretamente a estimativa do IPM quando esta é baseada em parâmetros biológicos do inseto. Por isso, múltiplos fatores devem ser considerados para que a perícia seja mais precisa. Com o aumento no número de mortes de animais de importância econômica devido à intoxicação medicamentosa, se faz necessárias pesquisas voltadas para a entomotoxicologia, uma área que carece de estudos específicos. Assim, o presente trabalho visou identificar a entomofauna associada a carcaças de cabras (Capra aegagrus hircus L.) mortas após tratamento com ivermectina, expostas em ambiente natural, além de averiguar possíveis diferenças na atratividade, no desenvolvimento dos imaturos que utilizaram esse substrato para alimentação e se a temperatura e o padrão de colonização da massa larval divergem entre as carcaças de animais mortos por intoxicação. Esse último parâmetro foi avaliado por meio de registros termográficos realizados em intervalos de 12 horas. Além da importância de fatores abióticos como luminosidade, temperatura, umidade e pluviosidade, pôde-se observar a ação da ivermectina nas carcaças tratadas, interferindo na composição da fauna colonizadora, no tempo total e em cada estágio da decomposição, assim como no padrão físico e comportamental das massas larvais em comparação ao grupo controle. Ainda foi demonstrado que a termografia pode ser utilizada como uma nova ferramenta em estudos periciais, auxiliando de forma significativa a avaliação dos parâmetros das massas larvais
Abstract: The estimation of the postmortem interval (PMI), period between the occurrence of death and the time at which the body or casing is found, is one of the main uses of insects in the forensic field. Using information on the biology, ecology and geographical distribution of insects, as well as the behavior of the entire fauna present in a body, is possible to estimate the time of death. Several factors such as temperature, humidity, presence of toxic substances in the tissues of a carcass, may interfere with the life cycle of an insect, directly affecting the estimate of PMI when it is based on biological parameters of the insect. Therefore, multiple factors should be considered so that the forensic analysis is more accurate. With the increase in the number of animal's deaths of economic importance due to drug intoxication, becomes necessary a research on entomotoxicology, an area with lack of specific studies. Thus, the present study aimed to identify the insect fauna associated with carcasses of goats (Capra aegagrus hircus L.) killed after treatment with ivermectin and exposed in the natural environment. Still, investigate possible differences in attractiveness, the immature development that used this substrate for feeding and if the temperature and the colonization pattern of larval mass differ between carcasses of animals killed after ivermectin inoculation. This last parameter was evaluated by thermographic shots performed at intervals of 12 hours. Besides the importance of abiotic factors such as luminosity, temperature, humidity and rainfall, the action of ivermectin on carcasses couse interferense in the composition of the colonizing fauna, the total time of colonization and the time of the decomposition stages, as well as the physical patterns and behavior of larval masses compared to the control group. Although it has been shown that thermography can be used as a new tool in forensic studies, helping to evaluate the parameters of larval mass
Mestrado
Parasitologia
Mestre em Parasitologia
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Alzeer, Samar Adnan. "Forensic toxicology of gamma hydroxybutyrate (GHB) metabolism." Thesis, University of Strathclyde, 2011. http://oleg.lib.strath.ac.uk:80/R/?func=dbin-jump-full&object_id=16779.
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Lourens, Denise. "The epidemiology, pathology and toxicology of suicide." Master's thesis, University of Cape Town, 1998. http://hdl.handle.net/11427/26780.
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Complete suicides and parasuicides are a major cause of death and disability in South Africa and the rest of the world. The epidemiology, pathology and toxicology of complete suicides were investigated in this study. All the complete suicide cases, which were presented to Salt River Medicolegal Laboratory over a period of one year (1 January 1997 - 31 December 1997), were analysed. The candidate personally conducted 148 of the alleged 180 suicide cases that presented in this time period (82%). The candidate did all the follow up investigations herself. The main findings were: 1. The male to female ratio was 5: 1. (131: 26) 2. Shooting and hanging were the most commonly used methods. 3. The racial distribution of violent deaths showed a high rate of suicides amongst the White population. 4. Suicides accounted for the Joss of young lives, the average age being 37,8 years. The mean age was 34 years. 5. Most victims committed suicide in and around their own homes. 6. The majority did not leave suicide notes. 7. Psychiatric disorders, poor health, arguments with close family members and friends, financial problems and long-standing relationship problems were the most common reasons for the suicides. 8. Suicides by prisoners accounted for 3,8% of the study (6 cases). 9. Two cases of double suicide (group suicide) were identified. 10. Five cases of homicide-suicide were identified in the study material. 11. One case of an attempted suicide by means of a high-speed motor vehicle accident, followed by the successful suicide by other means, was identified.
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Peterson, Kristina L. "Advances in flow extraction techniques : applications in forensic toxicology /." Thesis, Connect to this title online; UW restricted, 1997. http://hdl.handle.net/1773/11552.
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ZANCANARO, Flavio. "Mass spectrometry pneumatically assisted desorption/ionization in forensic toxicology." Doctoral thesis, Università degli Studi di Verona, 2010. http://hdl.handle.net/11562/342863.
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La spettrometria di massa è una delle tecniche più rilevanti in tossicologia clinica e forense. Il suo sviluppo e il miglioramento si basano sull'invenzione e l'uso di nuove sorgenti di ioni, nuovi metodi di ionizzazione, nuovi analizzatori di massa e nuove tecniche di pre-trattamento dei campioni. Una recente innovazione è la capacità di registrare spettri di massa su campioni reali direttamente nel loro ambiente nativo, senza preparazione del campione o pre-separazione. In questo ambito è stato descritto un nuovo metodo di ionizzazione/desorbimento chiamato DESI (desorbimento Electrospray ionizzazione), in seguito è stato sviluppato un metodo chiamato Dessì (Desorbimento Sonic Spray ionizzazione), a prima vista simile a DESI, ma in fondo sostanzialmente diverso. Questa tesi consiste nello sviluppo di una nuova interfaccia di desorbimento / ionizzazione per indagare il vero meccanismo coinvolto nella formazione di ioni, perché abbiamo ritenuto questo passaggio propedeutico per garantire il successivo uso del metodo in campo tossicologico analitico. Abbiamo verificato che il contributo pneumatico è preponderante per ottenere risultati. Quindi, la nostra nuova interfaccia di desorbimento/ionizzazione utilizza solo uno spray di solvente puro, senza alcuna tensione elettrica applicata allo sprayer. Un aspetto fondamentale di questo progetto, applicato a diverse matrici complesse, è il numero di parametri di funzionamento controllabili che possono essere studiati e ottimizzati per ottenere un'efficace analisi di superficie. Le variabili più importanti prese in considerazione sono state la geometria della sorgente (l'angolo di spray e l'angolo di diffusione di ioni, come pure le varie distanze nell'allineamento dello spray, del campione e dello spettrometro di massa) e la caratteristica dello spray (il contenuto del solvente ed il gas di portata). Tutte le misurazioni sono state eseguite in condizioni di ionizzazione positiva e negativa, variando tensione del capillare, pressione del gas di nebulizzazione, il flusso di gas al capillare e la temperatura del capillare. L'acquisizione è stata prodotta in modalità multiple mass spectra (MSn). Abbiamo applicato questa nuova soluzione tecnica per l'identificazione di composti tal quali, di principi attivi in campioni di farmaci mediante analisi diretta di compresse, principi attivi contenuti in specie vegetali. Gli sviluppi futuri saranno connessi ad applicare l’analisi diretta di analiti presenti sulle superfici originali di interesse nel settore tossicologico per il campionamento in vivo su superfici di tessuti, per individuare l’esposizione a farmaci e xenobiotici, oltre alla possibilità di costruire un’immagine chimica della distribuzione spaziale di analiti sulle superfici dei campioni.Mass spectrometry is one of the most relevant techniques in clinical and forensic toxicology. Its development and improvement are based on the invention and utilization of new ion sources, new ionization methods, new mass analyzers and new sample pre-treatment techniques. A recent innovation is the ability to record mass spectra on ordinary samples in their native environment, without sample preparation or pre-separation. In this field, a new desorption ionization method called DESI (Desorption Electrospray Ionization) has been described; subsequently, method called DeSSI (Desorption Sonic Spray Ionization), at first sight similar to DESI, but in deep substantially different, has been developed. This thesis consist in developing a new desorption/ionization interface to investigate the real mechanism involved in ions formation because we considered that propaedeutic for the extensive use of the method in the toxicological analytical field. We verified that the pneumatic contribution is preponderant to the obtained results. Hence, our new desorption/ionization interface uses only a spray of pure solvent with no high voltage on needle. A key aspect of this project, applied to several complex matrix, is the number of controllable operating parameters that can be investigated and optimized to obtain an efficient surface analysis. The most important variables are taken in consideration were the source geometry (the spray angle and the ion uptake angle, as well as the various distances in aligning the spray, sample and mass spectrometer) and the characteristic of sprayer (contents of the solvent spray and gas flow rate). All measurements have been performed in positive and negative ionization conditions, varying capillary voltage, nebulizing gas pressure, drying gas flow and end plate temperature. Acquisition was in multiple mass spectrometry mode (MSn). 2 We have applied this new technical solution to compound identification, active principles and drugs identification in direct tablet analysis, active principles and drugs identification in vegetable species. Future developments will be related to apply the direct analysis of analytes present on the original surfaces of interest in the toxicological field for in vivo sampling of living tissue surfaces, to identify drug and xenobiotic exposure, besides the chemical imaging of spatial distribution of analytes onto sample surfaces.
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Mullen, Carrie. "Quality Assurance of forensic investigations in toxicology and traffic safety." Thesis, University of Glasgow, 2014. http://theses.gla.ac.uk/5465/.
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The work described in this thesis deals with three aspects of quality assurance in the field of forensic toxicology: proficiency testing schemes, validation of analytical methods for the piperazine group of abused drugs and validation of the police field impairment test, used at the roadside to test drivers for drug-induced impairment. Proficiency Testing: Long term reviews were performed for two forensic external quality assurance schemes. Rounds 30 (in 2007) to 48 (in 2012) of the UKAS-accredited commercial Quartz Forensic Blood Toxicology Proficiency Testing Scheme (PTS), and a ten year period from 1999 to 2009 of the freely-available United Nations Office on Drugs and Crime (UNODC) International Collaborative Exercises (ICE). Only limited ICE data could be made available as much of the original data had been stored on a database which had become obsolete, hence the data were only available as the original results forms provided to UNODC by the ICE participants. Data was entered to Microsoft Excel® spreadsheets and Microsoft Access® databases from the original forms for the years 1999, 2001 (2 rounds), 2003 (2 rounds) and 2005 (2 rounds), and summary data was extracted from the UNODC round reports for the years 2007, 2008 and 2009. Four methods of scoring quantitative performance were reviewed and the most suitable, a z-score using an assigned ‘true’ value and a percentage of the true value as acceptable deviation, was applied to reanalyse the participants’ results and assess their performance. Methods of scoring proficiency which relied upon participants’ data to determine acceptable variation were found merely to describe the data rather than challenge participants on whether or not they were performing fit-for-purpose analyses. Factors such as participation, analytes tested, participants’ methods of analysis and participants performance were summarised for each scheme before the performance of the two schemes, and that of their participants, were compared. ICE tested more analytes per annum but from a smaller test menu than Quartz. This resulted in more repetitive testing and allowed for some trend analysis and performance monitoring. It was not possible to observe performance trends with Quartz due to the wide variety of analytes tested. The smaller array of potential analytes and more repetitive nature of ICE testing also meant that performance monitoring and detection of bias were easier to perform, and ICE was shown to be more effective as external quality assurance (EQA). Quartz provided a good educational resource as it incorporated the wide range of drugs which a forensic toxicology laboratory could realistically encounter. Following the review, however, it was recommended for QUARTZ that, to provide a safeguard against bias, more repetitive testing was required and this has now been adopted. Piperazines: All piperazine analogues are now illegal in the UK, registered as Class C of the Misuse of Drugs Act (1971) and schedule 2, part III of the Misuse of Drugs Regulations (2001). Piperazines can elicit similar effects to some ATS and methods for their detection should be available in forensic toxicology laboratories. In the present study, methods were developed for the detection of a range of piperazines in blood using LC-MS/MS (p-MeOPP, p-FPP, BZP, o-MeOPP, p-MPP and TFMPP) and GC-MS (p-FPP, BZP, TFMPP, p-MPP, o-MeOPP, m-CPP, p-MeOPP and p-CPP). Quality assurance required both methods to be validated. For all piperazine analytes accuracy was within ±15% (20% at low concentrations) and precision was within 15% (20% at low concentrations). For both methods LLOD of all analytes was 5 ng/ml of blood and upper limit of quantification was 2 µg/ml of blood. For the GC-MS method lower limits of quantification (LLOQs) were in the range 20 to 30 ng/ml of blood. For LC-MS/MS, LLOQs ranged from 50 to 60 ng/ml of blood, although quantification by the LC-MS/MS method was restricted by the lack of availability of appropriate internal standards. There were no apparent significant matrix effects and recovery by both methods was >60 % and, therefore, acceptable. Short term stability of the piperazine analytes was investigated. Piperazines remain sufficiently stable when stored in the fridge for at least one week, and are stable through three freeze-thaw cycles. There was no detectable degradation when blood samples were left on the bench-top or when extracted ‘in-process’ samples were left in the autosampler for up to 72 hours. The LC-MS/MS method could provide a readily applicable screening method. A small aliquot of a basic drug extract could be screened by LC-MS/MS for the presence of piperazines, leaving the majority of the extract for other analyses, for example, piperazines confirmation or amphetamines analysis. The GC-MS method was suitably validated to provide quantification but application to casework samples remains to be evaluated. It is recommended that piperazine testing be performed for all suspected MDMA or ‘club drug’ intoxication cases. The Field Impairment Test: The detection of drugged drivers primarily depends on the current method which is the driver field impairment test (FIT). FIT comprises measurement of pupil diameter and four physical tasks (the Romberg balance test, walk and turn test, one legged stand and finger to nose test) intended to simultaneously test comprehension, short term memory, balance and motor function. Despite FIT having ISO accreditation, it has been recognised that police officers lack confidence with the protocol and do not apply the test as often as is necessary. The main difficulty arises from the requirement to make a subjective judgement of impairment and officers lack confidence in their ability to do so. FIT has never been fully validated. The present study was designed to meet the urgent requirement to develop FIT into an objective measurement, by determining what constitutes “normal” performance in FIT by unimpaired adults of different ages. FIT performance was recorded for 79 individuals, a statistically determined cohort size, confirmed by breath and oral fluid analysis not to be under the influence of impairing substances. Each error made during FIT, as defined by the FIT standard operating procedure, was recorded and collated in a Microsoft Excel® spreadsheet for analysis. It was found that the definition of ‘errors’ was too stringent as many which are required to be recorded are normal physiological or behavioural characteristics, such as body sway, and most subjects would be unable to complete the task without displaying them. A less stringent, evidence-based definition of “error” was developed which allowed statistically more significant analysis to be performed on the FIT results. A statistically significant difference (P=0.00578) was shown to exist between the FIT performance of individuals under the age of forty years and those aged forty and over. Based on the principles of a PTS, robust mean and standard deviation were used to determine what constituted acceptable performance. Those in the younger age group could be considered impaired if the police officer witnessed more than seven errors, or, in the older age group, more than fifteen errors. Using these criteria the frequency of false positives, i.e. unimpaired drivers being assessed as impaired is estimated to be (less than 3%). Also, the ranges of errors observed in both groups was large and overlapped, such that it may be possible for an impaired person to appear unimpaired. This requires further investigation.
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Yokchue, Tanasiri. "In vitro studies of drug transformations : application to forensic toxicology." Thesis, University of Glasgow, 2016. http://theses.gla.ac.uk/7490/.
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The forensic toxicologist faces challenges in the detection of drugs and poisons in biological samples due to transformations which occur both during life and after death. For example, changes can result from drug metabolism during life or from the use of formalin solution for post mortem embalming purposes. The former requires the identification of drug metabolites and the latter the identification of chemical reaction products in order to know which substances had been administered. The work described in this thesis was aimed at providing ways of tackling these challenges and was divided into two parts. Part 1 investigated the use of in vitro drug metabolism by human liver microsomes (HLM) to obtain information on drug metabolites and Part 2 investigated the chemical reactions of drugs and a carbamate pesticide with formalin solution and formalin-blood. The initial aim of part I was to develop an in vitro metabolism method using HLM, based on a literature review of previous studies of this type. MDMA was chosen as a model compound to develop the HLM method because its metabolism was known and standards of its metabolites were commercially available. In addition, a sensitive and selective method was developed for the identification and quantitation of hydrophilic phase I drug metabolites using LC/MS/MS with a conventional reverse-phase (C18) column. In order to obtain suitable retention factors for polar drug metabolites on this column, acetyl derivatives were evaluated for converting the metabolites to more lipophilic compounds and an optimal separation system was developed. Acetate derivatives were found to be stable in the HPLC mobile phase and to provide good chromatographic separation of the target analytes. In vitro metabolism of MDMA and, subsequently, of other drugs involved incubation of 4 µg drug substance in pH 7.4 buffer with an NADPH generating system (NGS) at 37oC for 90 min with addition of more NGS after 30 min. The reaction was stopped at 90 min by the addition of acetonitrile before extraction of the metabolites. Acetate derivatives of MDMA metabolites were identified by LC/MS/MS using multiple reaction monitoring (MRM). Three phase I metabolites (both major and minor metabolites) of MDMA were detected in HLM samples. 3,4-dihydroxy-methamphetamine and 4-hydroxy-3-methoxymethamphetamine were found to be major metabolites of MDMA whereas 3,4-methylenedioxyamphetamine was found to be a minor metabolite. Subsequently, ten MDMA positive urines were analysed to compare the metabolite patterns with those produced by HLM. An LC/MS method for MDMA and its metabolites in urine samples was developed and validated. The method demonstrated good linearity, accuracy and precision and insignificant matrix effects, with limits of quantitation of 0.025 µg/ml. Moreover, derivatives of MDMA and its metabolites were quantified in all 10 positive human urine samples. The urine metabolite pattern was found to be similar to that from HLM. The second aim of Part 1 was to use the HLM system to study the metabolism of some new psychoactive substances, whose misuse worldwide has necessitated the development of analytical methods for these drugs in biological specimens. Methylone and butylone were selected as representative cathinones and para-methoxyamphetamine (PMA) was chosen as a representative ring-substituted amphetamine, because of the involvement of these drugs in recent drug-related deaths, because of a relative lack of information on their metabolism, and because reference standards of their metabolites were not commercially available. An LC/MS/MS method for the analysis of methylone, butylone, PMA and their metabolites was developed. Three phase I metabolites of methylone and butylone were detected in HLM samples. Ketone reduction to β-OH metabolites and demethylenation to dihydroxy-metabolites were found to be major phase I metabolic pathways of butylone and methylone whereas N-demethylation to nor-methylone and nor-butylone were found to be minor pathways. Also, demethylation to para-hydroxyamphetamine was found to be a major phase I metabolic pathway of PMA whereas β-hydroxylation to β-OH-PMA was found to be a minor pathway. Formaldehyde is used for embalming, to reduce decomposition and preserve cadavers, especially in tropical countries such as Thailand. Drugs present in the body can be exposed to formaldehyde resulting in decreasing concentrations of the original compounds and production of new substances. The aim of part II of the study was to evaluate the in vitro reactions of formaldehyde with selected drug groups including amphetamines (amphetamine, methamphetamine and MDMA), benzodiazepines (alprazolam and diazepam), opiates (morphine, hydromorphone, codeine and hydrocodone) and with a carbamate insecticide (carbosulfan). The study would identify degradation products to serve as markers for the parent compounds when these were no longer detectable. Drugs standards were spiked in 10% formalin solution and 10% formalin blood. Water and whole blood without formalin were used for controls. Samples were analysed by LC/MS/MS at different times from the start, over periods of up to 30 days. Amphetamine, methamphetamine and MDMA were found to rapidly convert to methamphetamine, DMA and MDDMA respectively, in both formalin solution and formalin blood, confirming the Eschweiler-Clarke reaction between amine-containing compounds and formaldehyde. Alprazolam was found to be unstable whereas diazepam was found to be stable in both formalin solution and water. Both were found to hydrolyse in formalin solution and to give open-ring alprazolam and open-ring diazepam. Other alprazolam conversion products attached to paraformaldehyde were detected in both formalin solution and formalin blood. Morphine and codeine were found to be more stable than hydromorphone and hydrocodone in formalin solution. Conversion products of hydromorphone and hydrocodone attached to paraformaldehyde were tentatively identified in formalin solution. Moreover, hydrocodone and hydromorphone rapidly decreased within 24 h in formalin blood and could not be detected after 7 days. Carbosulfan was found to be unstable in formalin solution and was rapidly hydrolysed within 24 h, whereas in water it was stable up to 48 h. Carbofuran was the major degradation product, plus smaller amounts of other products, 3-ketocarbofuran and 3-hydrocarbofuran. By contrast, carbosulfan slowly hydrolysed in formalin-blood and was still detected after 15 days. It was concluded that HLM provide a useful tool for human drug metabolism studies when ethical considerations preclude their controlled administration to humans. The use of chemical derivatisation for hydrophilic compounds such as polar drug metabolites for analysis by LC/MS/MS with a conventional C18 column is effective and inexpensive, and suitable for routine use in the identification and quantitation of drugs and their metabolites. The detection of parent drugs and their metabolites or conversion and decomposition products is potentially very useful for the interpretation of cases in forensic toxicology, especially when the original compounds cannot be observed.
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Tormey, William Patrick. "The provision of biochemical investigations in forensic toxicology for coroners." Thesis, Ulster University, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.646399.
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Death certification plays a central role in health service planning therefore identification of specific causes of death is critical. The requirements of biochemical toxicology as set out in the Coroners Acts in Ireland, Northern Ireland and England and Wales will be parsed to facilitate the construction of a modern best practice template for coroners' toxicology. The Royal College of Pathologists (RCPath) provides published standard guidelines for pathologists reporting to coroners. Their adequacy will be critically evaluated to facilitate reform with the intention of maximising the accuracy of death certification. The roles of psychological factors, tobacco smoking, non steroidal anti-inflammatory drugs, and cannabis in cardiac death will be detailed. The potential for adverse drug reactions to prescription medication to cause death by misadventure will be explored. The role for the expert witness in the inquisitorial coroners system to improve the accuracy of the causes of death and thus the verdict will be explored. My experience has shown that misinterpretation of presence of cannabis in autopsy blood and urine samples is common and this underlines the need for true expert guidance for the coroner. The current practice in biochemical toxicology of screening blood, urine and vitreous humor will be critically evaluated and the necessity for a wide ranging screen of potential toxins as a contributor to the cause of death examined. The appropriate analytes on the screening menu will be determined by local cultural factors. Gas and liquid chromatography with mass spectrometry are the methods of choice. The interpretation of isopropanol, ethanol and ketones in post-mortem blood will be considered as will t~e role of alcohol in death. The apparent population exposure to poisons as reported by Poisons Information Services will be used to explore the dichotomy between the usually benign outcome of common poisons and the often lethal consequences of poisoning by prescription and illicit drugs. The aim of this research is to use the template of the current legal requirements and routine laboratory procedures to suggest reforms which will improve the analytical protocol and reporting of biochemical toxicology in the coronial system resulting in greater accuracy in delineating the causes of death The narrative of this thesis travels through the areas of the coroners acts especially in the Republic of Ireland and the United Kingdom where forensic biochemistry plays a role in the specification of the causes of deaths. There is a deconstruction of the place of doctors in the coronial system and in the new arrangements following the passage of the Coroners and Justice Act 2009 in England and Wales and the potential for change in the Coroners Bill in the Republic of Ireland which fell with the dissolution of the Dail in20ll. There is an examination of the autopsy guidelines issued by the RCPath and suggestions for change which have been published. There is an analysis of the place of cannabinoids in coroners ' cases and publications setting out the position are included. A series of recommendations are made regarding improvement in practice for the reporting of biochemical toxicology in the coronial system. Two cases where there appears to be potential misinterpretation of the toxicological evidence, which may result in the review of the causes of death, are detailed as relevant clinical examples. Some laboratory pitfalls in relation to alcohol analysis have been demonstrated and the consequences of a protocol free service have been detailed with a prescription for improvement and practical solutions to improve outcomes. The under-estimation of the impact of tobacco toxicity is also addressed as is the potential for error due to lack of appreciation of drug-drug interactions. The role of biochemistry in the post-mortem diagnosis of alcoholic and diabetic ketoacidosis is discussed. Multidisciplinary reviews of biochemical toxicology for the coroners' court are suggested as the best safeguard of accurate interpretation to assist coronial enquiry. Conclusions suggesting standard operating procedures for post-mortem scenarios are detailed where possible.
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Swortwood, Madeleine Jean. "Comprehensive Forensic Toxicological Analysis of Designer Drugs." FIU Digital Commons, 2013. http://digitalcommons.fiu.edu/etd/997.
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New designer drugs are constantly emerging onto the illicit drug market and it is often difficult to validate and maintain comprehensive analytical methods for accurate detection of these compounds. Generally, toxicology laboratories utilize a screening method, such as immunoassay, for the presumptive identification of drugs of abuse. When a positive result occurs, confirmatory methods, such as gas chromatography (GC) or liquid chromatography (LC) coupled with mass spectrometry (MS), are required for more sensitive and specific analyses. In recent years, the need to study the activities of these compounds in screening assays as well as to develop confirmatory techniques to detect them in biological specimens has been recognized. Severe intoxications and fatalities have been encountered with emerging designer drugs, presenting analytical challenges for detection and identification of such novel compounds. The first major task of this research was to evaluate the performance of commercially available immunoassays to determine if designer drugs were cross-reactive. The second major task was to develop and validate a confirmatory method, using LC-MS, to identify and quantify these designer drugs in biological specimens.
Cross-reactivity towards the cathinone derivatives was found to be minimal. Several other phenethylamines demonstrated cross-reactivity at low concentrations, but results were consistent with those published by the assay manufacturer or as reported in the literature. Current immunoassay-based screening methods may not be ideal for presumptively identifying most designer drugs, including the “bath salts.” For this reason, an LC-MS based confirmatory method was developed for 32 compounds, including eight cathinone derivatives, with limits of quantification in the range of 1-10 ng/mL. The method was fully validated for selectivity, matrix effects, stability, recovery, precision, and accuracy. In order to compare the screening and confirmatory techniques, several human specimens were analyzed to demonstrate the importance of using a specific analytical method, such as LC-MS, to detect designer drugs in serum as immunoassays lack cross-reactivity with the novel compounds. Overall, minimal cross-reactivity was observed, highlighting the conclusion that these presumptive screens cannot detect many of the designer drugs and that a confirmatory technique, such as the LC-MS, is required for the comprehensive forensic toxicological analysis of designer drugs.
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Al-Ahmadi, Tareq Mohammed. "A comparison of derivatisation procedures for the detection of multiple analytes in systematic forensic toxicology." Connect to e-thesis, 2007. http://theses.gla.ac.uk/948/.
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Thesis (Ph.D.) - University of Glasgow, 2007.Ph.D. thesis submitted to the Department of Forensic Medicine and Science, University of Glasgow, 2007. Includes bibliographical references. Print version also available.
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Nilsson, Gunnel. "Zopiclone degradation in biological samples : Characteristics and consequences in forensic toxicology." Doctoral thesis, Linköpings universitet, Avdelningen för läkemedelsforskning, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-105821.
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Bio-analytical results are influenced by in vivo factors such as genetics, pharmacological and physiological conditions and in vitro factors such as specimen composition, sample additives and storage conditions. Zopiclone (ZOP) is a short-acting hypnotic drug (Imovane®) used for treatment of insomnia. ZOP is metabolized by three major pathways; oxidation to the active zopiclone N-oxide (ZOPNO), demethylation to the inactive N-desmethylzopiclone (NDZOP) and oxidative decarboxylation to other inactive metabolites. ZOP is increasingly being encountered in forensic cases and is a common finding in samples from drug-impaired drivers, users of illicit recreational drugs, victims of drug facilitated sexual assaults and forensic autopsy cases. ZOP is a notoriously unstable analyte in biological matrices and analytical results depend on pre-analytical factors, such as storage time and temperature. The overall aim of this thesis was to investigate the stability of ZOP and the factors of importance for degradation during storage in biological samples and to identify consequences for interpretation of results in forensic toxicology. In paper I, different stability tests in spiked samples were performed including short-term, longterm, freeze-thaw and processed stability. Analyses of ZOP were performed by gas chromatography with nitrogen phosphorous detection and ZOP concentrations were measured at selected time intervals. The degradation product 2-amino-5-chloropyridine (ACP) was identified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The stability investigations showed a very poor short-term storage stability of ZOP. Therefore, in paper II, the influence of pre-analytical conditions was further investigated in dosed subjects. Whole blood from volunteers was obtained before and after oral administration of Imovane®. In this study, the influence from physiological factors such as drug interactions, matrix composition and plasma protein levels were minimized. The results showed that ZOP was stable in whole blood for only one day at room temperature, one week in a refrigerator and at least three months frozen in authentic as well as in spiked whole blood. The rapid degradation of ZOP at ambient temperature can cause an underestimation of the true concentration and consequently flaw the interpretation. However, by also analyzing the degradation product ACP the original concentration of ZOP may be estimated. In papers III and IV, two LC-MS-MS methods were validated for the quantitation of ACP, ZOP and NDZOP in blood and ACP, ZOP, NDZOP and ZOPNO in urine. These methods were used in a controlled pharmacokinetic study where whole blood and urine were obtained after oral administration of Imovane®. Samples of blood and urine were aliquoted, analyzed and stored under different conditions and the formation of ACP was monitored. Additionally, at each studied time point the pH of the blood and urine samples was measured using i-STAT® system. The results showed that ACP was formed in equimolar amounts to the degradation of ZOP and its metabolites. In urine samples, the formation of ACP occurred at elevated pH or temperature and mirrored the degradation of ZOP, NDZOP and ZOPNO. The high concentrations of metabolites, which also degraded to ACP, made it impossible to estimate the original ZOP concentration. The results from analysis of blood samples containing ACP were also used to develop mathematical models to estimate the original ZOP concentration. Both models showed strong correlation to the original ZOP concentration (r=0.960 and r=0.955) with p<0.01. This study showed that the equimolar degradation of ZOP and NDZOP to ACP could be used to estimate the original concentration of ZOP in blood samples. Absence of ACP in the blood or urine samples analysed strongly suggests that degradation has not occurred and that the measured concentration of ZOP is reliable. For proper interpretation in forensic cases, it is strongly recommended that ZOP and its metabolites as well as ACP are included in the analysis.
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Takaichi, Kenichi. "Nail analysis in forensic toxicology for the detection of drug misuse." Thesis, University of Glasgow, 2004. http://theses.gla.ac.uk/3533/.
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This thesis examines the use of nail as an alternative biological specimen in forensic toxicology. Nail is a difficult analytical matrix from which to extract drugs because of its tough physical composition, based on keratin. The initial part of the project investigated the use of a cryogenic grinding method for fingernail clippings. Grinding at liquid nitrogen temperatures was found to be an effective procedure and the conditions were optimised to a two or three cycle programme of freezing and grinding. Small particle sizes were obtained of approximate size 1µm. It was established that drugs could be extracted directly from nail powder with a range of solvents without the need for alkaline hydrolysis. Methanol was found to be the most effective extraction solvent, which also gave the lowest number of co-extracted interfering compounds. This procedure was subsequently used with nail samples from different types of forensic cases, including cannabis, heroin and steroid abusers. Cryogenic grinding of nail was evaluated as an extraction method for cannabinoids in nail clippings from chronic cannabis smokers. This method was also compared to the alkaline hydrolysis method. Fingernail clippings were collected with prior informed consent from volunteers attending the Edinburgh Drug Addiction Study (EDAS) clinic. The collected nail clippings were decontaminated and divided into two groups: the first group was extracted with methanol after pulverisation in a liquid nitrogen cryogenic mill; the second was extracted with ethyl acetate after hydrolysis in sodium hydroxide. In both groups deuterated cannabinoids were used as internal standards. Both sets of extracts were derivatised with BSTFA before being analysed by gas chromatography – mass spectrometry (GC-MS). Cannabidiol, ?9-tetrahydrocannabinol and 11-hydroxy-?9-tetrahydrocannibinol were quantified in both sets of extracts. 11-nor-?9 –tetrahydrocannabinol-9-carboxylic acid was only identified and quantified in the extracts resulting from the cryogenic grinding method. Cannabinoid concentrations were very low, in the range 0-4 ng/mg. These results strongly support the use of nail as a biological specimen for the detection and quantification of past exposure to cannabis, and secondly, they indicate that grinding with a cryogenic mill is a useful procedure, which yields simultaneous results for the primary psychoactive cannabinoid and its metabolites. Cryogenic grinding was then evaluated for the extraction of opioids in nail in comparison with the conventional alkaline hydrolysis method. Finger and toe nails were collected from donors with informed consent.
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Ariffin, Marinah Mohd. "The application of novel extraction and analytical techniques in forensic toxicology." Thesis, University of Glasgow, 2006. http://theses.gla.ac.uk/4144/.
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The aim of this study was to investigate new methods of analysis which might be applied to forensic toxicology problems including those resulting from pesticides, particularly the quaternary ammonium herbicide group, and from drugs, particularly the benzodiazepine group. In the first part of this study, an efficient method for the determination of quaternary ammonium (QA) compounds (pesticides and drugs) in human whole blood was developed. The second part of this study concerned the development of a novel sorbents for solid phase extraction using molecularly imprinted polymers (MIPs). The approach adopted was initially to synthesise a known MIP using diazepam as template then to prepare novel MIPs using other benzodiazepines and analogues of QA compounds as templates. In the first of these stages, an anti-diazepam MIP was synthesized using methacrylate acid (MAA) as the monomer and ethylene glycol dimethacrylate (EGDMA) as the cross-liner and was then ground and prepared for use as an SPE sorbent by packing it into SPE cartridges. These cartridges were used to clean up extracts of diazepam and other benzodiazepine drugs made from hair samples via a molecularly imprinted solid-phase extraction (MISPE) protocol. The MISPE method was also found to be applicable to the analysis of diazepam metabolites and other benzodiazepine drugs in addition to diazepam itself. The application of the extraction method to post-mortem hair samples yielded results that were in good agreement with ELISA data (from blood samples) and data arising from the analysis of the same blood samples using a validated in-house SPE-LC-MS-MS method. The MISPE procedure was also compared with a conventional SPE method for analysis of benzodiazepines in hair samples. The results from MISPE protocol showed better selectivity, specificity and accuracy toward diazepam (template molecule) and other benzodiazepines that display a similar resemblance to diazepam in terms of molecular structure. The MISPE procedure was found to be simpler and to offer cleaner extracts compared to a conventional SPE method.
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Gerostamoulos, Jim 1969. "The toxicological interpretation of heroin-related deaths." Monash University, Dept. of Forensic Medicine, 1997. http://arrow.monash.edu.au/hdl/1959.1/7770.
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Spinelli, Eliani. "Identificação de usuários de Cannabis por cromatografia em camada delgada de alta eficiência." Universidade de São Paulo, 1994. http://www.teses.usp.br/teses/disponiveis/9/9137/tde-12122014-171458/.
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A análise de fluidos biológicos para detecção de usuários de Cannabis não é rotina em nossos serviços de toxicologia forense pela falta de um método aplicável às condições de trabalho desses laboratórios. Neste trabalho foi estudado um método que utiliza a cromatografia de camada delgada de alta eficiência (CCDAE) como técnica de identificação. Cinco mililitros de urina são submetidos à hidrólise alcalina e à extração Iíquido/líquido, com posterior aplicação do resíduo obtido na cromatoplaca. O limite de detecção em estudo realizado com adicionados foi de 5ng/ml. Urina de usuários de Cannabis quando submetidas a esta metodologia apresentaram resultado semelhante ao do padrão de THCCOOH, principal produto de biotransformação do THC. As amostras utilizadas como branco de referência não apresentaram mancha semelhante. Na análise das amostras de usuários por imunoensaio de fluorescência polarizada (\"cutoff\' 50ng/ml) obteve-se resultado negativo para usuários moderados e ocasionais. Com auxilio de curva-padrão observou-se que a concentração provável de canabinóides nessas amostras estaria entre 20-50ng/ml. No estudo comparativo dos resultados obtidos nas duas técnicas, foi verificada uma correspondência de 100% para as amostras de usuários com padrão de uso intenso. Nos usuários moderados e ocasionais não foi observada boa correspondência entre os resultados.Abstract not available.
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Curtis, Byron Dale. "The forensic toxicology of 2,5-dimethoxy-4-n-propylthiophenethylamine (2C-T-7)." Oklahoma City : [s.n.], 2005.
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Lemos, Nikolaos P. "Analysis of bile and nail as alternative biological specimens in forensic toxicology." Thesis, University of Glasgow, 1999. http://theses.gla.ac.uk/4116/.
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This thesis examines the use of bile and nail as alternative biological specimens in forensic toxicology. In chapter 1, a brief overview of the mechanisms of substance passage into and out of membranes and fluids and matrices was presented followed by a review of the use of alternative biological specimens for analytical purposes. The experimental part of this thesis begins in chapter 2 where a simple and rapid method for the detection and quantification of dextropropoxyphene in bile and its major metabolite, norpropoxyphene, is presented. Following this, nail is examined as an alternative biological specimen in cases of medico-legal interest. Firstly, two major cannabinoids, 9-tetrahydrocannabinol and 11-nor-9-tetrahydrocannabinol-9-carboxylic acid were identified in the nail (chapter 3) by means of RIA and GC-MS. Cannabinoids were found to be present in all six cases that were analysed for cannabinoids by RIA and their concentration ranged from 0.23 ng/mg to 2.80 ng/mg (average: 1.03 ng/mg). Using GC-MS, 9-tetrahydrocannabinol was detected in 11 out of the 14 nail clipping hydrolysates after basic extraction with concentrations ranging from 0.13 ng/mg to 6.97 ng/mg (average: 1.44 ng/mg). 11-nor-9-tetrahydrocannabinol-9-carboxylic acid was not detected in any of these nail clipping hydrolysates but was detected in two of the three fingernail clipping hydrolysates extracted under acidic pH with concentrations ranging from 9.82 ng/mg to 29.7 ng/mg (average: 19.8 ng/mg). In chapter 4, the detection and quantification of diazepam, the most commonly encountered benzodiazepine, were described. Using ECD-GC, diazepam was detected in hydrolysates of all 6 sets of nail clippings in concentrations ranging from 4.37 to 87.8 ng/mg (average: 25.7 ng/mg). In chapter 5, an analytical protocol for the detection and quantification of morphine in nail clippings of known heroin abusers was presented. Finally, a protocol for the detection and quantification of methadone in nail clippings of patients attending a methadone maintenance program was presented.
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Allen, Desiree Lisa. "The applications of supercritical fluid and solid-phase extraction techniques for the recovery of drugs of abuse from biological matrices." Thesis, University of Glasgow, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.249963.
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Haikney, Tarryn. "Investigation into DNA recovered from human teeth for forensic applications." Master's thesis, Faculty of Health Sciences, 2020. http://hdl.handle.net/11427/32223.
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In South Africa, there is a burden of unidentified deceased individuals in forensic mortuaries. When human remains are severely compromised, hard tissues may provide the only DNA source for identification. The QIAamp® DNA Investigator Kit is used in forensic laboratories worldwide, including in South Africa, to extract DNA for identification purposes. However, in local forensic casework, the DNA recovered from teeth is often of insufficient quantity and quality for generating a DNA profile. The phenol-chloroform DNA extraction method has demonstrated improved, yet inconsistent results, when used on hard tissues. Therefore, this study assessed DNA recovery from 52 human control teeth from three deceased individuals, using an optimised phenol-chloroform method. This method involved an overnight demineralisation, two additions of phenol/chloroform/isoamyl alcohol (25:24:1) and an ethanol precipitation, as used by the Australian Federal Police. Quantitative PCR (Quantifiler™ Trio DNA Quantification Kit) and DNA profiling (PowerPlex® ESI 16 System) were then used to assess DNA quantity and quality. Results were compared to those obtained from the same teeth but extracted using the QIAamp® DNA Investigator Kit. The phenol-chloroform method recovered DNA with significantly higher yields (p = 0.0454) and significantly less degradation (p < 0.0001). Despite this improvement, there was no significant difference in DNA profiling success. This study also did a preliminary analysis of other factors affecting results and suggested that premolars might be the best tooth type with regards to DNA quantity, quality and profiling. Furthermore, dental disease and jawbone had a significant impact on results from teeth. Lastly, the phenol-chloroform method was applied to six teeth from a marine decomposition case to assess its performance in a local forensic setting. DNA metrics were particularly poor in this casework example, highlighting how different forensic and control environments are and the need for further optimisation. Overall, this study supports the use of the phenol-chloroform method and has provided a preliminary suggestion of the best tooth type, jawbone and tooth condition for DNA analysis for forensic human identification.
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Torrance, Hazel Jennifer. "An investigation into the potential use of liquid chromatography:mass spectrometry in forensic toxicology." Thesis, University of Glasgow, 2005. http://theses.gla.ac.uk/4122/.
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The aim of this project was to evaluate the use of LC-MS in the forensic toxicology setting. To investigate if its use could solve problems encountered while using other instrumentation including downtime, limits of detection, chromatography and specificity. Benzodiazepines as a class, are known for their undesirable chromatographic behaviour when using GC. Using LC-MS two models were developed for the analysis of these drugs in whole blood. Increasing awareness of drug facilitated sexual assault, has led to an increase in the number of cases to be analysed for drugs such as Rohypnol®. This prompted the development and validation of a sensitive and specific method for its detection in blood using solid phase extraction and liquid chromatography – mass spectrometry. To enhance the qualitative data and cope with degraded samples, the use of LC-MS was used in the analysis of diazepam and its three metabolites. A method was developed and validated and is now used in the routine analysis of blood samples in the laboratory. The LC-MS proved invaluable in the analysis of sildenafil, Viagra®, in a post-mortem blood sample received in the laboratory. A single quadrupole mass spectrometer was used to develop and validate a method to determine if the dose was therapeutic or toxic. The use of oral fluid as an alternative specimen to blood or urine was investigated. This was through the British Roadside Impairment Test Evaluation (BRITE) project. LC-MS in combination with GC-MS was used to screen for over 50 licit and illicit drugs in 1mL of oral fluid. LC-MS-MS was then used to identify and quantitated 21 drugs of abuse and their metabolites using a similar sample size. The use of one extraction and the reliability of LC-MS proved invaluable in these projects.
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Morrison, Calum M. "Chiral and achiral analysis of benzodiazepine and anti-anginal drugs in forensic toxicology." Thesis, University of Glasgow, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.321443.
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Kashkary, Loay M. T. "Development of a combined DNA and drug extraction methodology for forensic toxicology application." Thesis, University of Hull, 2014. http://hydra.hull.ac.uk/resources/hull:11661.
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Biological samples recovered at crime scenes may contain unsuspected and valuable evidence, such as illicit drugs, in addition to nucleic acids. Deoxyribonucleic acid (DNA) analysis provides valuable information to identify a suspect or victim, as well as to exclude an innocent individual as the perpetrator of a crime. Identification of drugs can also be very informative for forensic investigation to determine whether a perpetrator committed a crime under the influence of illicit substances. In the field of forensic analysis, sample preparation for identifying both DNA and drugs of abuse represents a challenge due to limited sample quantity and only trace levels of target analytes present in the matrices. As a result, an analytical approach has been developed to enable the combined extraction of DNA and four amphetamines (amphetamine [AM], methamphetamine [MA], 3,4-methylenedioxyamphetamine [MDA], and 3,4-methylenedioxymethamphetamine hydrochloride [MDMA]) from a small amount of sample (50 μl) using a single extraction procedure. This study has focused on solid-phase extraction (SPE) using inorganic silica-based matrices as sorbents to facilitate such sample processing. The advantages of using inorganic silica-based monoliths are due to the simple fixation of the material in a column or within a microfluidic device, their mechanical stability with organic solvents, the availability of simple surface modifications to enable the desired chemical interaction with the target molecules, and a unique bimodal structure that allows a large surface area with minimum back pressure. A dual-phase SPE method was developed consisting of silica beads modified with octadecyl groups packed inside a luer lock adapter for amphetamine extraction coupled in series with a silica-based monolith for DNA extraction within a microfluidic system for a fully combined genetic and drug extraction system. The proposed method was effective for the extraction of the target drugs from a spiked buffer and artificial urine giving an average recovery greater than 70% and 50%, respectively, with high reproducibility (˂ 15% RSD). The limits of detection were 0.6 μg ml⁻¹ for AM and MA, 0.7 μg ml⁻¹ for MDA, and 0.8 μg ml⁻¹ for MDMA with linear calibration curves between 0.625 and 20 μg ml⁻¹. The method was also able to extract DNA from the spiked TE buffer and urine sample with average extraction efficiencies of 36% and 30%, respectively, which were successfully amplified via the polymerase chain reaction (PCR). The proposed method is not only suitable for the combined extraction of DNA and amphetamines from a limited sample size, but also reduces sample handling and potential contamination. This method could, in future, be applied to anti-doping analysis for the detection of doping agents and conducting DNA profiling as evidence to ascertain whether samples belong to the right athletes.
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Almeida, Rafael Menck de. "Redistribuição postmortem de barbitúricos em tecidos biológicos humanos." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/9/9141/tde-12032013-160134/.
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Os barbitúricos são fármacos com atividade depressora do sistema nervoso central e estão relacionados com elevados números de casos de intoxicações e uso não-médico em vários países. No Brasil, a droga antiepiléptica mais encontrada em casos de intoxicação é o fenobarbital, pois os pacientes relatam que \"essa é uma substância com ação forte no cérebro\". De fato, os barbitúricos estão altamente relacionados com tentativa de suicídio e homicídio. Nesses casos existe a necessidade da quantificação dessas substâncias para correlacionar com a causa mortis. No entanto, as análises toxicológicas postmortem são de difícil execução e interpretação, pois a concentração de agentes tóxicos encontrados é bastante complexa e afetada não só pela condição de deterioração do corpo, mas também por um processo conhecido como redistribuição postmortem. Em geral, concentrações mais elevadas são encontradas no sangue situado nos sítios centrais (como o sangue coletado da cavidade cardíaca) em comparação aos níveis verificados nos vasos periféricos (como a veia femoral). Em outros casos, o tempo entre a morte e o exame postmortem é suficiente para que algumas substâncias que normalmente estariam presentes no sangue não estejam mais disponíveis neste fluido biológico. Há ainda um agravante, pois não existem valores de referências para a maioria das amostras biológicas não-convencionais, dificultando assim a interpretação dos resultados. Os exames toxicológicos devem ser realizados em amostras biológicas e tem como objetivo a avaliação da intoxicação como circunstância qualificadora do delito, como causa de periculosidade ou imputabilidade. O objetivo deste trabalho foi o desenvolvimento e aplicação de métodos de identificação de barbitúricos (butalbital, secobarbital, pentobarbital e fenobarbital) em amostras postmortem (sangue cardíaco, sangue femoral e fígado). Os analitos foram extraídos das amostras utilizando a micro extração em fase líquida (LPME), identificados e quantificados por cromatografia em fase gasosa acoplada à espectrometria de massas (GC-MS). Após o desenvolvimento e validação, os métodos analíticos foram aplicados em amostras postmortem de onze cadáveres necropsiados pelo Serviço de Verificação de Óbito da Cidade de São Paulo (SVO (SVO-USP), com suspeita de envolvimento de barbitúricos. Nove casos apresentaram resultado positivo para fenobarbital. A média da razão sangue femoral/sangue cardíaco foi de 0,91 com o desvio padrão de 0,23. Para a correlação fígado/sangue femoral a média foi de 1,17 com desvio padrão de 1,29. Os barbitúricos foram escolhidos como modelo de estudo devido à grande incidência de casos de intoxicação aguda com estes fármacos no Brasil.Barbiturates are a class of drugs that act as central nervous system depressant and are associated with high numbers of poisoning cases and non-medical use in several countries. In Brazil, phenobarbital is the most related antiepileptic drug involved in intoxication cases. Patients report that \"this drug is a substance with strong action in the brain.\" In fact, barbiturates are highly related to attempted suicide and homicide cases, in which quantification of these substances to correlate with the possible cause of death is necessary. However, postmortem toxicological analyses are difficult to perform and interpret, because the concentration of toxic agents found is quite complex and affected not only by deterioration condition of the body but also by a process known as postmortem redistribution. In general, higher concentrations are found in the blood located in central sites (e.g. heart cavity) compared with the levels found in peripheral vessels (such as the femoral vein). In other cases, the time between death and postmortem examination is enough for some substances that would normally be present in the blood are no longer available in this biological fluid. Besides, there are few reference values for most non-conventional biological samples, making it difficult to interpret the results. The objective of this work was the development and application of methods for identification of barbiturates (butalbital, secobarbital, pentobarbital and phenobarbital) in postmortem samples (heart blood, femoral blood and liver). The analytes were extracted by using liquid-phase micro extraction (LPME) and quantified by gas chromatography-mass spectrometry (GC-MS). After the development and validation, analytical methods were applied in real cases of eleven corpses autopsied by Death Verification Service of São Paulo City (USP-SVO), with suspected of barbiturates involvement. Nine cases were positive for phenobarbital. The mean ratio of blood femoral / cardiac blood was 0.91 with a standard deviation of 0.23. For the correlation liver / femoral blood the average was 1.17 with a standard deviation of 1.29. Barbiturates were chosen as model for this study because the high incidence of cases of acute poisoning with these drugs in Brazil.
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du, Toit Chante. "Retrospective analysis of abandoned live births, stillbirths and non-viable foetuses admitted to Salt River Mortuary, Cape Town." Master's thesis, University of Cape Town, 2018. http://hdl.handle.net/11427/29883.
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The abandonment of neonates in locations where discovery and survival is not intended is a global concern. These cases comprise non-viable foetuses and stillbirths (natural deaths), as well as abandoned live births (unnatural deaths); the latter having possible legal consequences. To describe the profile of abandoned neonates and obtain a global perspective of the post-mortem investigation in such cases, a systematic review of the literature on abandoned foetuses, concealed births and neonaticide was conducted. This revealed a paucity of research on the subject; only one published South African study and less than 30 studies from other parts of the world were obtained. While guidelines were available, a standard protocol for conducting the medico-legal investigation on abandoned neonates did not exist and the necessary extent of the investigation was debated. Furthermore, seemingly higher rates of abandoned neonates were observed in South Africa compared to elsewhere in the world, warranting investigation of these cases in a local setting. In an attempt to add to the data concerning abandoned neonates in South Africa, a case file review was carried out on abandoned live births, stillbirths and non-viable foetuses at Salt River Mortuary between 1 January 2012 and 31 December 2016 (n=249). Despite the majority of the cases being natural deaths, the cause of death frequently remained 'undetermined’ in these cases, often due to the presence of decomposition. Histological analyses were only performed in a small fraction of undetermined cases. Furthermore, the hypothesis that the prosecution rate of abandoned live births is extremely low was supported by this study, with only one case prosecuted in the 5- year period. For the remainder of the cases, the court status was given as either 'under investigation’ (47.8%) or 'case closed’ (47.8%). In the majority of the instances, the case was closed due to the unknown identity of the biological mother; however, DNA analyses were not performed in all of these cases. Overall, the data highlighted the need for the development and implementation of standard protocols, to ensure that cause of death and identification of the neonate can be established as far as possible.
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Holmgren, Per. "Postmortem toxicology : aspects on interpretation /." Linköping : Univ, 2004. http://www.bibl.liu.se/liupubl/disp/disp2004/med862s.pdf.
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Subhahar, Michael. "Pharmacokinetics and pharmacodynamics of some NSAIDs in horses : a pharmacological, biochemical and forensic study." Thesis, University of Central Lancashire, 2013. http://clok.uclan.ac.uk/9244/.
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Non-steroidal anti- inflammatory drugs (NSAIDs) have been in use for over 100 years to treat pain, exerting their analgesic effect by inhibiting prostaglandin (PG) synthesis via the COX pathway. Some of the NSAIDs have adverse side effects including ulceration of the stomach and cardiovascular events which are associated with bleeding. Search is still going on to find a safe NSAID. Two new coxib NSAIDs, namely celecoxib and etoricoxib have been developed and they exert marked beneficial effects in reducing pain in humans and other small animals with little or no side effects. No such study has been done on horses to see if they can tolerate the drug as an analgesic pain killer. This study was designed to investigate the effects of the two coxib NSAIDs, celecoxib and etoricoxib in six retired race horses to determine any adverse side effects of the drugs, the time course changes in their metabolism and elimination once administered orally in known physiological doses and the metabolites produced by each drug over time. The study employed well established clinical and biochemical techniques to measure blood-borne parameters and the metabolism of each drug. The results show that either etoricoxib or celecoxib had no adverse side effects on blood borne parameters and the stomach of the horses. Pharmacokinetic study following oral administration of 2 mg/kg b wt of either celecoxib or etoricoxib to the six race horses showed a Cmax of 1.15 ± 0.3 µg/ml, tmax, to be 4.09 ± 1.60 hr and a terminal half- life of 15.52 ± 1.99hr for celecoxib and a Cmax of 1.0± 0.09 µg/ml, tmax of 0.79 ± 0.1 hr and, terminal half- life of 11.51 ± 1.56 hr, respectively for etoricoxib. The results also show that each coxib is metabolized in the horse and both the parent drug and its metabolites are found in the urine, plasma and faeces. The results have also shown that even small traces of either drug or its metabolites can be measured in urine samples even 120 hours following oral administration. The main metabolites found in plasma, urine and faeces are hydroxyl celecoxib and carboxycelecoxib when celecoxib was administered orally to the 6 retired race horses. Similarly, hydroxymethyletoricoxib, carboxylic etoricoxib, hydroxymethyl-1-N-oxide metabolite of etoricoxib and hydroxymethyletoricoxib glucuronide were also found in plasma, urine and faeces following oral administration etoricoxib .to the animals. The results for either horse haeptocytes or camel liver show to some extend similar metabolites. In conclusion, the results show that both drugs have no adverse side effects in the horse and their metabolites are completely eliminated within 120 hours following oral administration.
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Al-Ahmadi, Tareq Mohmmed. "A comparison of derivatisation procedures for the detection of multiple analytes in systematic forensic toxicology." Thesis, University of Glasgow, 2007. http://theses.gla.ac.uk/948/.
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Three different derivatisation procedures were evaluated for their general applicability to systematic toxicological analysis (STA) involving (a) acylation with pentafluoropropionyl anhydride (PFPA) and pentafluoropropanol (PFP-OH), (b) acylation/esterification (methylation) with pentafluoropropionyl anhydride (PFPA) and a novel methylating agent trimethylsilyldiazomethane (TMS-diazomethane), used as a chromatographic derivatisation reagent for the first time in this study, and (c) silylation with tertiary-butyldimethylsilyl-trifluoroacetamide (MTBSTFA). Model compounds were selected for the evaluation process including a primary amine (amphetamine), a secondary amine (methamphetamine), alicyclic and aromatic hydroxy compounds (morphine, tetrahydrocannabinol), and carboxylic acids (benzoylecgonine, 11-nor tetrahydrocannabinol-9-carboxylic acid). For method (a) derivatisation was successful for all of the test compounds and mass spectra were obtained for each of them. For method (b), the novel methylating agent trimethylsilyl-diazomethane was used to convert carboxylic acids into the corresponding methyl esters. This reaction was found to proceed rapidly and quantitatively at room temperature and holds potential for future use in toxicology to replace diazomethane, a hazardous and toxic material. Method (c) gave derivatives with all test compounds except the secondary amine, methamphetamine, and the alcohol, morphine. The gas chromatographic behaviour of these derivatives was good and the mass spectra had prominent ions suitable for GC-MS-SIM. The extraction of multiple drugs from blood was evaluated using the novel polymeric SPE sorbent Strata-X. The same test compounds were used to assess the extraction step in terms of recovery and variation (within day and between days). The extracts were analysed by GC-MS-SIM using each of the three types of derivative. Recoveries of the test compounds were in the range of 50-100 percent depending on the analyte and its concentration in blood. All calibration curves were linear and had correlation coefficients higher than 0.99. Within day variations and between day variations were in the range of 2-22% relative standard deviation. Limits of detection and quantitation were measured for the model compounds and were found to be in the ranges of 0.4-7.3 ng/ml and 1.1-24.4 ng/ml respectively. The full method, combining extraction with each of the derivatisation reactions was finally evaluated for the presence of interferences with real case blood samples. The three derivatisation procedures were evaluated using four test compounds comprising diazepam plus its three metabolites nordiazepam, temazepam and oxazepam. The hydroxylated metabolites (temazepam and oxazepam) formed derivatives readily with all three reagent mixtures but nordiazepam (secondary aromatic amine) did not react except with MTBSTFA. Based on the work of this study it is concluded that a method is possible for STA based on a polymeric sorbent, to give a general extract, followed by a generalised derivatisation procedure such as acylation, with PFPA/PFP-OH prior to GC-MS.
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Battah, Abdel-Kader Hamdi. "The analysis of drugs and solvents in forensic toxicology by combined GC- and LC-MS." Thesis, University of Glasgow, 1989. http://theses.gla.ac.uk/4115/.
Full textAbstract:
The work described in this thesis was in the field of Forensic Toxicology, which is the study and practice of toxicology for legal purposes. Three different application areas were considered: (a) the analysis of drugs in blood by gas chromatography-mass spectrometry (GC-MS) following isolation from the biological matrix by solid phase extraction procedures, (b) the analysis of paint solvents in blood by gas chromatography (GC) and GC-MS following dynamic headspace elution from blood, and (c) an evaluation of Thermospray/Plasmaspray (TSP/PSP LC-MS) liquid chromatography-mass spectrometry as the basis of drug screening techniques in forensic toxicology. (a) In the first of these areas, a sensitive, specific and reliable method was developed for the analysis of basic drugs in blood, using morphine and buprenorphine as model compounds which are also drugs commonly abused in the Glasgow area. A novel extraction procedure was used, based on a commercially available chemically-modified silica containing surface-bound benzenesulphonylpropyl groups, which served as a cation exchange resin. Several methods for the initial treatment of the biological matrix wre examined and the one selected involved absorption of the blood sample on diatomaceous earth and solvent elution of the crude extract containing any drugs present in the sample. This extract was then purified using the cation exchange resin: conditions suitable for the efficient retention of basic drugs and subsequent elution were also examined and developed. The extraction efficiencies for morphine were 925% and 954% at concentrations of 35 and 560ng/ml blood, respectively, for buprenorphine 836% and 875% , at concentration of 0.5 and 8ng/ml respectively, and for other drugs were better than 85% . The end-step analytical technique chosen for this method was GC-MS, because of analytical and legal requirements with respect to sensitivity and specificity. The polar nature of the model compounds, and of many other drugs likely to be encountered in this field, required chemical modification of the substances prior to gas chromatography. A comparison was made of three silyl ether derivatives - the trimethylsily (TMS), ethyldimethylsilyl (EMS) and tert-butyldimethylsilyl (MTBS) ethers. The conditions required for derivative formation were examined, including the choice of silyl donor reagent, solvents, temperature of reaction and time to completion. The EDMS donor, diethyltetramethyldisilazane, was selected on the basis of the midl reaction conditions required for the test compounds and also because this reagent caused less interference during GC-MS analysis. EDMS ethers gave satisfactory gas chromatographic behaviour and the presence of prominent ions at high mass was shown to be advantageous for specific and sensitive detection by SIR-MS with little background interference. The developed method was considered to be useful for both clinical and post-mortem blood samples containing morphine and buprenorphine down to the low picogram/millilitre level, and therefore adequate for the intended purpose. The method was subsequently applied to 13 samples submitted for analysis to the Department of Forensic Medicine and Science and found to be satisfactory. (b) In the second area of application, dynamic head space (DHS) elution was used for the analysis of paint solvents in blood. Volatilised solvents were trapped on a Tenax-GC cartridge and were subsequently analysed by GC-MS. The extraction efficiency of this method for C18-C12 n-alkane hydrocarbons, which were present in the paint materials, was better than 90% and sensitivity down to pg/ml levels was obtained. Solvent extraction procedures for these hydrocarbons were evaluated using high purity solvent. The extraction efficiency was better than 85% . Analysis of extracts by GC or GC-MS suffered from interference from the solvent front which reduced the sensitivity. The DHS method was applied to a pilot study for occupational monitoring of a group of painters to assess the presence of paint solvents in their blood. Two venous blood samples were collected at the beginning and at the end of a working week from each subject. They showed the presence of several solvents similar to those present in paint material and the levels in the second series of samples were higher than those of the first series. The differences between the levels in the two series were statistically significant for n-nonane, n-undecane and alkylbenzenes. The levels in the first sample indicated incomplete clearance of these solvents from the body during the weekend, and the second samples indicated solvent uptake during the working week. Solvent contamination in the extraction system was tackled by several approaches but still hindered the accurate estimation of solvent levels in blood. (c) In the third area of application, the operating parameters which control the sensitivity of the mass spectrometer using the TSP/PSP LC-MS interface were evaluated. These included the effects of the probe temperature and discharge voltage on sensitivity and mass spectral fragmentation pattern and the effects of the mobile phase constituents on sensitivity and mass spectral peak stability. Solvent systems containing ammonium acetate buffer and an organic modifier such as acetonitrile produced the best results in plasmaspray LC-MS. Three model HPLC-MS analyses were developed for mixtures of basic drugs, barbiturates and opiates using both the plasmaspray positive and negative ion modes. During the development of the mobile phases, the optimization of chromatography by organic modifiers was assessed. The quality of chromatography obtained was not always as good as expected in conventional HPLC, but the combination of chromatographic and mass spectral data could be used for identification and quantification purposes. A compilation of PSP mass spectra of drugs commonly encountered in forensic toxicology was produced. These mass spectra provided mostly molecular weight information with little structural information.
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Al, Jaber Jaber. "Forensic and clinical toxicology studies focusing on drug analysis in hair and other biological matrices." Thesis, Queen Mary, University of London, 2013. http://qmro.qmul.ac.uk/xmlui/handle/123456789/8507.
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Clinical and forensic toxicology analysts rely heavily in their daily tests on the analysis of the conventional samples (blood and urine). However, these specimens are limited in the time scale they reflect with regard to drug intake history and also in terms of drug stability within the matrices. Alternative matrices such as hair, oral fluids and dried blood spots (DBS) provide new horizons and new opportunities. Drugs incorporated within hair are very stable. Hair also provides a very long detection window, for at least one year, if not a lot longer. Oral fluids on the other hand are non-intrusive, easy to collect and much cleaner sample matrix than blood or urine. DBS also offer great drug stability, are easy to collect, faster to analyse and suitable for automated analysis. However, a number of studies are needed to assess the limits of these alternative samples in terms of the correlation of their results with the results of conventional samples and with regard to drug stability. Such studies will enable a more reliable and confident interpretation of results obtained from these matrices especially for medico-legal purposes. The main aims of this research were: to develop and validate analytical methods for detection and quantitation of drugs of use and abuse in hair, oral fluids, blood and DBS samples, to investigate the correlation between dose and drug concentration in hair, blood and oral fluids after controlled chronic drug administration, to investigate the stability of anti-psychotic drugs in DBS (from patients) stored under different conditions and the effect of addition of preservative, and to investigate the alcohol intake prevalence among Kuwaiti drug addicts and correlate these results with selfreported intake. As the majority of drugs were basic, an extraction method based on methanolic incubation was developed for detection of basic/weak basic drugs in hair. It was compared to alkaline digestion (with NaOH) followed by liquid-liquid extraction (LLE). Detection was achieved by LC-MS/MS (Sciex2000) after separation on a C18 column. When applying both methods on positive authentic hair samples the results showed that the methanolic method was capable of extracting most basic drugs in hair but only partially, while the alkaline digestion method was found to degrade V some unstable drugs like sulpiride, but was capable of fully extracting the alkaline stable drugs such as quetiapine. After development and validation of the LLE-LC-MS(Exactive) method for the analysis of anti-psychotics in blood, oral fluids and hair, an investigation was carried out on the correlation pattern between trough concentrations in those three matrices. The most significant correlation coefficients (r) found were those between blood and hair concentrations, procyclidine r=0.83 (18 subjects p=<0.001), risperidone r=0.96 (14 subjects p=<0.001), haloperidol r=0.90 (10 subjects p=<0.001), OH-risperidone r=0.24 (13 subjects p=>0.44), quetiapine r=0.28 (14 subjects p=>0.33) and chlorprothixene r=0.32 (13 subjects p=>0.32). Among the interesting results was the strong correlation found between drugs half-lives and the mean ratio of hair concentration/dose (r=0.96, p=<0.003). The stability of anti-pyschotics in DBS from patients’ samples was assessed by storing them at four different temperatures (25, 4, -20 and -80°C) with and without prior impregnation of the DBS cards with sodium fluoride. After development and validation of the LLE-LC-MS method, samples were analysed at days 0, 45, 90 and 180. Results showed good stability of all the compounds (procyclidine, quetiapine, risperidone, OH-risperidone, chlorprothixene and haloperidol) in all the different storage conditions and no significant increase or decrease in drug concentrations with sodium fluoride impregnation. Finally, after trials with five different HPLC columns, two SPE cartridges, two LLE extraction procedures and two mass spectrometer instruments, a method was developed and validated for the detection and quantitation of alcohol’s minor and specific metabolite in hair, ethyl glucuronide (EtG). The method has a limit of detection (LOD) of 3pg/mg and lower limit of quantitation (LLOQ) of 9pg/mg. This method was applied to 59 hair samples from patients at a general addiction centre and alcohol prevalence was investigated and its correlation with self-reported use was investigated.
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Rafael, Venson. "Hollow-fibre liquid-phase microextraction : investigation into the potential use in clinical and forensic toxicology." Thesis, University of Glasgow, 2017. http://theses.gla.ac.uk/8697/.
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Hollow-fibre liquid-phase microextraction (HF-LPME) was introduced in 1999 as a miniaturised version of liquid-liquid extraction (LLE) in order to reduce the consumption of organic solvents and offer an environmentally-friendly approach to extraction procedures. Since then, several studies have been published in the field of forensic and clinical toxicology applying the technique to a broad range of analytes; however more studies are necessary regarding its applicability to bioanalyses. The principle of HF-LPME is the extraction of analytes across a thin supported liquid membrane within the walls of a hollow fibre from a donor phase (DP) into an acceptor phase (AP). It is an extraction technique that encompasses several parameters that require optimisation for an efficient method; this is most effectively achieved by utilising a design of experiment (DoE) approach rather than the conventional one-factor-at-a-time (OFAT) approach. The main aim of this work is to further investigate the applicability of HF-LPME to the fields of forensic and clinical toxicology by developing and validating methods to extract various drugs from different biological matrices. Complex matrices, such as whole blood, are commonly used in forensic toxicology. Considering that not many studies have been performed on the application of HF-LPME to whole blood (only 10 up to the present day), this is an aspect that requires further investigation. For this, a fast, accurate and precise 3-phase HF-LPME method followed by LC-MS/MS analysis was developed and validated to simultaneously quantify 5 NBOMe drugs in human whole blood. NBOMe drugs are a group of substances part of the so-called “novel psychoactive substances” (NPS); drugs that have been emerging with increasing frequency over the last few years. NBOMes are associated to deaths as the causa mortis, and due to their high potency, these drugs are normally abused in micrograms. For that reason, the HF-LPME method developed had to present high sensitivity (LOD of pg/mL). The aim of the second part of this project was to challenge HF-LPME further by developing and validating methods to assess the potential application of HF-LPME in multi-drug analyses. Urine was selected as biological matrix, and the group of chosen analytes were 14 anti-hypertensive drugs and their metabolites with very different physical-chemical properties. HF-LPME has never been applied to such a broad spectrum of substances in previous bioanalytical studies. These drugs were divided into two groups (acidic and basic/neutral), and a total of four extraction methods (two for each group of analytes) were developed and optimised using chemometrics (DoE) then analysed by LC-MS/MS. Two of these methods were liquid-liquid extraction (LLE) methods that were developed and validated to be used as reference to which the two HF-LPME methods were compared. The LLE methods were sensitive, accurate, precise, and valid for application to real case samples. The HF-LPME methods presented some limitations due to the lack of isotopically-labelled analogues of each specific analyte as internal standards (IS); for non-exhaustive methods the use of these IS should be adopted as standard practise. Real urine samples from genuine patients were extracted using all 4 methods followed by LC-MS/MS analysis. By applying the methods to real case samples, it was possible to define that the HF-LPME methods were suitable for qualitative screening of urine to determine the level of compliance of patients under anti-hypertensive pharmacotherapy. However, for quantification of the drugs applying HF-LPME, further development is required to incorporate the use of isotopically labelled analogues. This study proved that HF-LPME is a potential asset not only for forensic but also for clinical toxicology. It can be a very powerful tool which, mainly due to its green-chemistry approach and pre-concentration capabilities, which allows direct injection into the analytical instrument, could potentially become a more used technique in the future. However, the analyst should be careful when developing HF-LPME methods, to bear in mind its limitations so that methods that are fit-for-purpose can be developed.
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Al-Asmari, Ahmed Ibrahim. "Applications of LC-MS/MS in forensic toxicology for the analysis of drugs and their metabolites." Thesis, University of Glasgow, 2009. http://theses.gla.ac.uk/1290/.
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This thesis studied opioids and alcohol in forensic toxicology by LC-MS/MS, which avoids time-consuming procedures involving hydrolysis, extraction and derivatisation. Initially, a method was validated for quantification of opioids and unhydrolysed polar metabolites in autopsy specimens and was used to develop procedures for interpretation of forensic toxicology results. The LC-MS/MS method developed has been validated for the simultaneous determination of 24 opioids in human whole blood, including, for the first time in human whole blood, naloxone-3-glucuronide. Although a large number of drugs of interest were included in the method, acceptance criteria for linearity, precision, and recovery for all analytes were achieved. The method was found useful for differentiating between users of heroin and other opioids, such as codeine and morphine, and for determining the survival time in deaths attributed to heroin use. Subsequently, the efficiencies of hydrolytic and non-hydrolytic methods for opioid analysis were compared for buprenorphine (BUP) analysis. The aims were to develop and validate a method for the direct determination (DM) of buprenorphine (BUP), norbuprenorphine (NBUB), buprenorphine-3-glucuronide (B3G) and norbuprenorphine-3-glucuronide (NBUP3G). This method was compared with an in house enzymatic hydrolysis method (HM) for the determination of total buprenorphine (TBUP) and norbuprenorphine (TNBUP), using real positive BUP urine case samples. A comparison between the drug and metabolite concentrations obtained by direct and hydrolysis methods was reported for the first time in this work. LC-MS analysis was also applied to paediatric plasma specimens obtained from a clinical pharmacokinetic study of intravenous and intranasal administration of diamorphine. This work was aimed at obtaining pharmacokinetic data for diamorphine and its metabolites in children following intravenous (IVDIM) and intranasal (INDIM) administration in a blind study. It was intended that the concentrations of active metabolites would be used to evaluate whether or not IN-DIM can deliver rapid and efficient analgesia in children comparable to that obtained with IV-DIM. The pharmacokinetics of DIM and its metabolites following INDIM and IVDIM administration in children have been compared for the first time in this study, which confirmed that INDIM can achieve therapeutic plasma concentrations of active metabolites, although these were lower than those obtained with IVDIM and occur at later times after administration. In Scotland, the number of prescriptions for oxycodone has risen by 430% since prescribing began in 2002. Blood samples from fatalities in the West of Scotland involving oxycodone were analysed using an LC-ESI-MS/MS method developed for the determination of oxycodone and its metabolites in post-mortem specimens. To the author’s knowledge, this is the first report of blood and urine concentrations of noroxycodone and oxymorphone in acute oxycodone overdoses. Also, it is the first LC-MS/MS application to be reported with oxycodone related fatalities cases in forensic toxicology as most of previous reports used GC or HPLC applications. Moreover, this work reported for the first time vitreous humour levels of noroxycodone following oxycodone intoxication. Ten oxycodone-related deaths were identified in the short period of this study in the Strathclyde region of Scotland alone, highlighting the importance of including this drug in routine laboratory screening and confirmation procedures. Polar alcohol metabolites ethyl glucuronide and ethyl sulfate are biomarkers of ante-mortem alcohol consumption and are used to test for post-mortem artefactual formation of alcohol. An LC-MS method for these metabolites using a novel hydrophilic interaction liquid chromatography column was validated and applied to routine forensic casework. Ninety urine case samples were divided into three groups depending on the ethanol concentration found in blood and analysed by the developed method: group A with post-mortem blood ethanol higher than 200 mg/100 mL; group B with ethanol concentration in the range 80 to 200 mg/100 mL and group C with ethanol concentration less than 80 mg/100 mL. It was concluded that the risk of false positive ethanol results increased in the low ethanol concentration group as several cases tested negative for both biomarkers. ETG was detected at low concentrations in some cases for which ETS tested negative, suggesting that either ETG may have a longer half-life in urine or else ETS is unstable. The data was compared with previous studies and confirmed that both ethanol biomarkers should be determined in heavily putrefied cases and when the ethanol level in post-mortem blood is low, suggesting the production of ethanol after death. To the authors’ knowledge, this is the first report of the determination of ETS using an LC-ESI-ion trap-MS/MS method, and of a HILIC-ESI-ion trap-MS/MS method for the simultaneous determination of ETG and ETS in post-mortem urine samples.
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Wells, Krystal. "Ideal chromatography separation and detection for determination of various anions in biological samples for forensic toxicology." Thesis, Wells, Krystal (2020) Ideal chromatography separation and detection for determination of various anions in biological samples for forensic toxicology. Masters by Coursework thesis, Murdoch University, 2020. https://researchrepository.murdoch.edu.au/id/eprint/56600/.
Full textAbstract:
The nitrogen and sulfur cycles are of growing significance in the scientific fields due to their biological processes. Both cycles have positive metabolic outcomes when in normal concentrations and conditions, however excessive intake of the inorganic anions each have fatal consequences. Concentrations of either nitrate and/or nitrite or sulfide beyond normal levels in results in toxicity, and which may result in death. Therefore, a simple, time sensitive and accurate method for the determination and quantitation of nitrite and/or nitrate and sulfide is required in the field of post-mortem toxicology, to aid in cause of death investigations. Unfortunately, several suicide cases are related to the excessive intake of nitrate and nitrite by overdose of the anions by medicine or curing salts and deaths involving car exhaust fumes also have high nitrite/nitrate levels in the deceased’s system. Due to the short half-life of nitrate in blood samples, nitrate is often required to be detected and quantitated after being converted to nitrite. With sulfide poisonings, sulfide is difficult to isolate and quantitate, so detection methods look for the metabolite thiosulfate in blood and urine samples. To the best of the authors knowledge, no recent papers have been published reviewing and comparing the methods applicable to human biological fluids since 2005. This review provides background on nitrate/nitrite and sulfide roles in biological systems, consequences of excess intake, and the current methodologies available for detection and quantitation of these anions. It was found that chromatographic methods, specifically gas chromatography mass-spectrometry and liquid chromatography mass-spectrometry, were most commonly used in forensic labs for the detection and quantitation of each anion.
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Tremori, Tália Missen [UNESP]. "Cães e gatos: expressão das lesões em intoxicações criminais." Universidade Estadual Paulista (UNESP), 2015. http://hdl.handle.net/11449/131926.
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000851905.pdf: 816079 bytes, checksum: f6b22c768507fec25ab121a9695360f9 (MD5)Os casos de intoxicações não intencionais ou intencionais são comuns na história da Medicina Veterinária principalmente em animais de companhia como cães e gatos. A Medicina Veterinária Legal utiliza amplo conhecimento para fundamentar laudos técnicos que tem como função auxiliar processos judiciais. De acordo com o artigo 32 da Lei de Crimes Ambientais 9.605 de 12 de fevereiro de 1998, intoxicar animais é crime de maus tratos. O reconhecimento adequado dos sinais clínicos, lesões anatomopatológicas características dos casos de intoxicação que levam á óbito associados com os métodos de identificação laboratorial de toxicologia forense, são fundamentais para estabelecer um diagnóstico definitivo do agente tóxico. No presente trabalho objetivou-se ampliar os estudos na área de Medicina Veterinária Legal e identificar lesões anatomopatológicas decorrentes de intoxicação em cães e gatos. No período de 2009 a 2014 foram selecionados do arquivo da Faculdade de Medicina Veterinária e Zootecnia, UNESP - Universidade Estadual Paulista, Campus de Botucatu, Departamento de Clínica Veterinária, Serviço de Patologia Veterinária, 42 casos, sendo 31 (73,8%) cães e 11 (26,2%) gatos. Destes casos 21 (50%) apresentaram Boletim de Ocorrência e 22 (52,4%) realizaram exame toxicológico. A maior prevalência foi de intoxicações por carbamato. O exame necroscópico revelou que a as principais causa mortis foram insuficiência cardiorrespiratória e choque hipovolêmico. No exame histopatológico de fígado, rim e encéfalo as principais lesões observadas foram congestão, degeneração e hemorragia. Os órgãos apresentaram sinais de autólise e putrefação. As técnicas diagnósticas utilizadas são complementares e auxiliam o Médico Veterinário a elaborar laudos técnicos para processos judiciais nos casos de intoxicações criminais
The cases of poisoning no intentional or intentional are common in the history of the Veterinary Medicine mainly in animals of company as dogs and cats. The Legal Veterinary Medicine use these tools in the base of technical decisions to aid processes, involving crimes with animals. According to the Law of Environmental Crimes 9.605 of February 12 of 1998, poisoning in animals is considered crime of mistreatments. The appropriate recognition of the clinical signs, lesions anatomical pathological that characterizes the cases of intoxication that take to death associated with the methods of identification laboratorial of forensic toxicology is fundamental to establish a definitive diagnosis of the toxic agent. In the present work was made analysis of lesions relation of toxic agents and context of Veterinary Forensic Medicine in these situations. In period 2009 to 2014 are selected from the archive of Faculdade de Medicina Veterinária e Zootecnia, UNESP - Universidade Estadual Paulista, Campus de Botucatu, Departamento de Clínica Veterinária, Serviço de Patologia Veterinária 42 cases, 31 (73,8%) dogs and 11 (26,2%) cats. These cases 21 (50%) feature Boletim de Ocorrência and 22 (52,4%) are made toxicologycal exam. The highest prevalence ware intoxication for carbamate. The necropsy revealed that main causa mortis were cardiac respiratory insufficiency and hypovolemic shock. In histopathology of liver, kidney and brain the main lesions are congestion, degeneration and bledding. The organs show signs of autolysis and putrefaction. The diagnostic technics used are additional and help veterinarion to make reports for litigation in cases of criminal intoxication
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Tremori, Tália Missen. "Cães e gatos : expressão das lesões em intoxicações criminais /." Botucatu, 2015. http://hdl.handle.net/11449/131926.
Full textAbstract:
Orientador: Noeme Souza RochaBanca: Elan Cardozo Paes de Almeida
Banca: Alexandre Hataka
Resumo: Os casos de intoxicações não intencionais ou intencionais são comuns na história da Medicina Veterinária principalmente em animais de companhia como cães e gatos. A Medicina Veterinária Legal utiliza amplo conhecimento para fundamentar laudos técnicos que tem como função auxiliar processos judiciais. De acordo com o artigo 32 da Lei de Crimes Ambientais 9.605 de 12 de fevereiro de 1998, intoxicar animais é crime de maus tratos. O reconhecimento adequado dos sinais clínicos, lesões anatomopatológicas características dos casos de intoxicação que levam á óbito associados com os métodos de identificação laboratorial de toxicologia forense, são fundamentais para estabelecer um diagnóstico definitivo do agente tóxico. No presente trabalho objetivou-se ampliar os estudos na área de Medicina Veterinária Legal e identificar lesões anatomopatológicas decorrentes de intoxicação em cães e gatos. No período de 2009 a 2014 foram selecionados do arquivo da Faculdade de Medicina Veterinária e Zootecnia, UNESP - Universidade Estadual Paulista, Campus de Botucatu, Departamento de Clínica Veterinária, Serviço de Patologia Veterinária, 42 casos, sendo 31 (73,8%) cães e 11 (26,2%) gatos. Destes casos 21 (50%) apresentaram Boletim de Ocorrência e 22 (52,4%) realizaram exame toxicológico. A maior prevalência foi de intoxicações por carbamato. O exame necroscópico revelou que a as principais causa mortis foram insuficiência cardiorrespiratória e choque hipovolêmico. No exame histopatológico de fígado, rim e encéfalo as principais lesões observadas foram congestão, degeneração e hemorragia. Os órgãos apresentaram sinais de autólise e putrefação. As técnicas diagnósticas utilizadas são complementares e auxiliam o Médico Veterinário a elaborar laudos técnicos para processos judiciais nos casos de intoxicações criminais
Abstract: The cases of poisoning no intentional or intentional are common in the history of the Veterinary Medicine mainly in animals of company as dogs and cats. The Legal Veterinary Medicine use these tools in the base of technical decisions to aid processes, involving crimes with animals. According to the Law of Environmental Crimes 9.605 of February 12 of 1998, poisoning in animals is considered crime of mistreatments. The appropriate recognition of the clinical signs, lesions anatomical pathological that characterizes the cases of intoxication that take to death associated with the methods of identification laboratorial of forensic toxicology is fundamental to establish a definitive diagnosis of the toxic agent. In the present work was made analysis of lesions relation of toxic agents and context of Veterinary Forensic Medicine in these situations. In period 2009 to 2014 are selected from the archive of Faculdade de Medicina Veterinária e Zootecnia, UNESP - Universidade Estadual Paulista, Campus de Botucatu, Departamento de Clínica Veterinária, Serviço de Patologia Veterinária 42 cases, 31 (73,8%) dogs and 11 (26,2%) cats. These cases 21 (50%) feature Boletim de Ocorrência and 22 (52,4%) are made toxicologycal exam. The highest prevalence ware intoxication for carbamate. The necropsy revealed that main causa mortis were cardiac respiratory insufficiency and hypovolemic shock. In histopathology of liver, kidney and brain the main lesions are congestion, degeneration and bledding. The organs show signs of autolysis and putrefaction. The diagnostic technics used are additional and help veterinarion to make reports for litigation in cases of criminal intoxication
Mestre
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Costa, José Luiz da. "Eletroforese capilar como ferramenta analítica para toxicologia forense." Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/46/46133/tde-23092008-104730/.
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No primeiro capítulo deste trabalho, são apresentados aspectos gerais sobre toxicologia forense e sobre a eletroforese capilar, onde se buscou mostrar como a técnica analítica pode ser útil para aplicações forenses. O segundo capítulo apresenta o desenvolvimento de metodologia analítica baseada em eletroforese capilar com detecção por arranjo de diodos para determinação de drogas de abuso ou seus produtos de biotransformação em humor vítreo. Foram estudados parâmetros como a composição do eletrólito de corrida (com especial atenção ao fenômeno de eletrodispersão), pré-concentração online (stacking) e modo de extração dos analitos. Foi obtida completa separação eletroforética de 12 analitos investigados em menos de 10 minutos de corrida. Os parâmetros de confiança analítica do método mostraram este é perfeitamente aplicável às análises toxicológicas com finalidade forense. O terceiro capítulo apresenta a elaboração de metodologia analítica baseada em eletroforese capilar acoplada a espectrometria de massas para determinação de cocaína e cinco produtos de biotransformação em urina, com procedimento de preparo da amostra biológica simplificado. O procedimento desenvolvido apresentou sensibilidade adequada para verificação de intoxicações agudas por cocaína, e a espectrometria de massas acrescentou grande seletividade à análise, principalmente quando a detecção foi realizada pela seleção do íon-pai e fragmentos gerados a 34% de energia de colisão. O terceiro capítulo apresenta o desenvolvimento de método simples e rápido para determinação de MDMA em comprimidos de Ecstasy usando eletroforese capilar de zona. Na corrida eletroforética desenvolvida, é possível determinar a concentração de MDMA em menos de dois minutos (usando procaína com padrão interno). O método desenvolvido foi comparado ao utilizado rotineiramente no Núcleo de Análise Instrumental do Instituto de Criminalística de São Paulo, baseado em cromatografia líquida de alta eficiência com detecção por fluorescência. O método eletroforético desenvolvido foi cinco vezes mais rápido do que o método de referência, permitindo maior produtividade sem que houvesse perda da qualidade do resultado. Por fim, o capítulo 4 apresenta as considerações finais deste trabalho, onde se pode concluir que a eletroforese capilar, ainda que pouco utilizada em laboratórios forenses brasileiros, pode ser ferramenta de grande utilidade nas análises toxicológicas destinadas a esta finalidade.In the first chapter of this thesis, general aspects on forensic toxicology and capillary electrophoresis are presented, aiming to show how the analytical technique can be useful for forensic applications. The second chapter presents the development of analytical methodology based on capillary electrophoresis with diode array detection for determining drugs of abuse and/or their biotransformation products in vitreous humor. Parameters such as the composition of background electrolyte (with special attention to the phenomenon of electrodispersion), online pre-concentration (stacking) and sample preparation procedures were objects of study. The complete electrophoretic separation of 12 investigated analytes was obtained within 10 minutes of run. The validation parameters of the method have shown that this is perfectly applicable to toxicological analyses with forensic purposes. The third chapter presents the elaboration of analytical methodology based on capillary electrophoresis coupled to mass spectrometry for determining cocaine and five biotransformation products in urine, with simple sample preparation. The process developed presented adequate sensitivity for the verification of acute intoxications by cocaine, and mass spectrometry contributed with great selectiveness to the analysis, mainly when the detection was conducted by the selection of the molecular-ion and fragments generated at 34% of collision energy. The fourth chapter presents the development of a simple and quick method for determining MDMA in tablets of Ecstasy using capillary zone electrophoresis. In the running condition, it is possible to determine the concentration of MDMA in less than two minutes (using procaine with internal standard). The method developed was compared with the one routinely used at Núcleo de Análise Instrumental do Instituto de Criminalística de São Paulo, based on high performance liquid chromatography with fluorescence detection. The electrophoretic method developed was five times faster than the reference one, allowing higher productivity without loss of quality in the result. Finally, chapter five presents the final considerations of this thesis, where it is possible to conclude that capillary electrophoresis, even being little utilized in Brazilian forensic laboratories, can be a tool of great utility in toxicological analyses destined to this purpose.
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Bévalot, Fabien. "Intérêts et limites de la bile et de l'humeur vitrée comme matrices alternatives en toxicologie médicolégale." Thesis, Lyon 1, 2014. http://www.theses.fr/2014LYO10362/document.
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Ce travail avait pour objectif d'étudier l'intérêt et les limites de l'analyse de deux matrices alternatives que sont la bile et l'humeur vitrée (HV), en toxicologie médicolégale. Pour chacune des deux matrices, une revue de la littérature visait à investiguer les connaissances utiles à leur application en toxicologie médicolégale. Une place importante de ces revues est réservée à l'anatomie et la physiologie de l'HV et du système biliaire ainsi qu'aux mécanismes de distribution des xénobiotiques dans ces matrices. La partie expérimentale décrit trois études: deux menées sur populations autopsiques et une associant expérimentations animales et études de populations autopsiques. Les deux premières ont permis de proposer des outils statistiques d'interprétation des concentrations de méprobamate mesurées dans ces matrices. Ils peuvent être utilisés dans diverses situations à la place ou en complément de l'interprétation des concentrations sanguines: cadavre exsangue, putréfaction avancée du corps, redistribution post mortem des xénobiotiques… La troisième étude concernait six molécules (diazépam, citalopram, cyamémazine, morphine, caféine et méprobamate). Les molécules détectées dans le sang l'étaient systématiquement dans l'HV et la bile aussi bien dans les prélèvements des populations autopsiques que ceux issus des expérimentations animales. Les concentrations vitréennes chez l'animal et chez l'homme étaient systématiquement corrélées aux concentrations sanguines, exceptées celles de cyamémazine et de citalopram chez l'homme. Pour la bile, une corrélation significative était observée pour le méprobamate et la caféine chez l'homme et l'animal. Il ressort de ces résultats, que l'analyse de l'HV et de la bile permettent de disposer d'informations relatives à la nature des molécules absorbées et à leur rôle dans la survenue du décèsThe present study sought to assess the interest and limitations of analyzing two alternative matrices, bile and vitreous humor (VH), in forensic toxicology. For each matrix, a literature review established the state of knowledge relating to their forensic application. The review placed special focus on the anatomy and physiology of VH and the biliary system and the mechanisms of xenobiotic distribution within the specific matrix. The experimental sections describe three studies: two performed on autopsy populations, and one associating autopsy populations to an animal model. The first two studies resulted in statistical tools for interpreting meprobamate concentrations in these matrices, which can be used as alternatives or complements to blood concentrations in various situations: exsanguination, advanced putrefaction, postmortem xenobiotic redistribution, etc. The third study focused on 6 molecules: diazepam, citalopram, cyamemazine, morphine, caffeine and meprobamate. Molecules detected in blood were also systematically detected in VH and bile samples from both the autopsy and animal populations. Animal VH and blood levels showed systematic correlation. In autopsy samples, cyamemazine and citalopram showed no such correlation. In bile, significant correlations with blood concentrations were found for meprobamate and caffeine in both the autopsy and animal populations. This study confirmed the interest of postmortem analysis of bile and VH. Results show that analyzing bile and VH sheds light on drugs intake and on their implication in cause of death
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Santos, Júnior Júlio César 1985. "Novas técnicas analíticas aplicadas a drogas de abuso presentes em humor vítreo." [s.n.], 2014. http://repositorio.unicamp.br/jspui/handle/REPOSIP/312948.
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Orientadores: Nelci Fenalti Höehr, Marcos Nogueira EberlinDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Embora as anfetaminas estejam proibidas no Brasil, elas continuam sendo adquiridas ilegalmente assim como os canabinóides e cocaína, que representam um dos principais problemas de saúde pública a serem enfrentados no nosso país. Um dos grandes desafios desta área é a dificuldade de obtenção de material para exames periciais. O humor vítreo por encontrar-se isolado em um compartimento relativamente protegido de contaminação externa, invasão de microorganismos e traumatismos em geral, bem como por sua simplicidade/estabilidade analítica e esterilidade durante um longo período após a morte constitui-se como uma excelente amostra para a determinação de xenobióticos em corpos politraumatizados, carbonizados ou em decomposição, auxiliando na delegação da causa mortis. O uso da espectrometria de massas e o advento de novas metodologias de ionização são ferramentas essenciais à toxicologia forense, a V-EASI (venture easy ambient sonic-spray), é uma fonte de ionização de fácil aplicação e instalação, que não requer fluxo de eluente e os demais fatores utilizados nas fontes comerciais. Além disso, o uso da espectrometria de massas de ressonância ciclotrônica de íons por transformada de Fourier (FT-ICR-MS) de ultra-alta resolução e exatidão (valores de m/z exatos) leva a exata composição molecular, alcançando erros abaixo de 1 ppm (partes-por-milhão). Perante isso a avaliação da fórmula molecular normalmente é inequívoca. Quando acoplada a ionização por eletrospray (ESI) espécies moleculares suaves são formadas reduzindo a complexidade do espectro e produzindo informação composicional livre de fragmentos em misturas complexas facilitando sua compreensão. Portanto este trabalho visa o desenvolvimento de metodologias analíticas para análise de drogas de abuso presentes em humor vítreo, empregando o uso de técnicas modernas de espectrometria de massas (FT-ICR-MS e V-EASI-MS)
Abstract: Although amphetamines are banned in Brazil, they remain illegally acquired as cannabinoids and cocaine, which account for a public health task to be faced in this country. The major challenge is to obtain material for investigation exams. The vitreous humor constitutes a good alternative for these exams, since it occurs isolated in a protected space, free of external contamination and of microorganisms and traumatisms, and also due to its analytical stability and sterility preserving it for a long period after death. Moreover, the vitreous humor constitutes an excellent sample for the determination of xenobiotics even in polytraumatized bodies, carbonized or in decomposition, involved in the causa mortis. The use of mass spectrometry and the advent of new ionization methods are essential tools for forensic toxicology, the V-EASI (venture easy ambient sonic-spray), is a source of ionization easy to use and install, not requiring nitrogen flow, eluent flow and other factors used in commercial sources. Furthermore, the use of Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) provides ultra high resolution and accuracy in mass analysis and its accurate m/z values lead to the exact molecular composition, reaching errors below 1 ppm (parts-per-million) on normal operational conditions, the assigned molecular formula are normally unequivocal. When electrospray ionization (ESI) is used, soft molecular species are formed reducing spectra complexity and providing fragment-free compositional information about complex mixtures facilitating comprehension. Therefore, this work aims at the development of analytical methodologies for the analysis of drugs of abuse present in the vitreous humor, employing the use of modern techniques of mass spectrometry (FT-ICR-MS and V-EASI-MS
Mestrado
Ciencias Biomedicas
Mestre em Ciências Médicas
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Carvalho, Virgínia Martins. "Redistribuição da cocaína e sua influência na neuroquímica post mortem." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/9/9141/tde-15072011-120720/.
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A interpretação dos achados laboratoriais no estabelecimento da causa mortis consiste na integração dos conhecimentos sobre a toxicocinética e toxicodinâmica do agente, conhecimentos de sua redistribuição post mortem (RPM) e achados necroscópicos que possibilitem o nexo causal entre o toxicante e o efeito letal. Neste sentido, é importante considerar que somente as concentrações de cocaína (COC) e seus metabólitos podem não ser determinantes na interpretação da causa de morte, podendo ser útil o cotejamento com outros parâmetros, como os níveis de neurotrasmissores que representem o mecanismo de ação do fármaco. Assim, este trabalho teve por objetivo investigar a RPM da COC e seu metabólito benzoilecgonina (BE) em três segmentos do tecido encefálico (TE), no humor vítreo (HV) e sangue (SG), bem como determinar as concentrações de catecolaminas e indolaminas no encéfalo para avaliar a aplicação da neuroquímica post mortem (NPM) na toxicologia forense. No estudo de RPM foram quantificados os níveis de COC e BE em três segmentos do TE (córtex frontal, núcleos da base e cerebelo), no HV e no SG através de método por cromatografia líquida de alta eficiência (HPLC) acoplada ao detector de arranjo de diodos. Os estudos de neuroquímica foram realizados empregando-se HPLC acoplada ao detector eletroquímico. Os resultados indicaram que as concentrações médias de COC foram maiores no TE, seguido por SG e HV (3,09, 2,92 e 1,71 µg/mL, respectivamente), enquanto para BE foram maiores em SG, seguido por HV e TE (6,12, 1,39 e 0,87 µg/mL, respectivamente). As concentrações de COC se apresentaram distribuídas uniformemente nos três segmentos de TE e apresentaram alta correlação com o HV. Adicionalmente, a média de concentrações de dopamina total foi maior no grupo de indivíduos com amostras positivas para COC, sendo verificado diferença significativa entre este grupo e o de indivíduos com amostras negativas para o fármaco de interesse. Os resultados demostraram que o estudo de RPM e da NPM constituem ferramentas aplicáveis na interpretação da causa e maneira de morte.In case of intoxication, the interpretation of analytical results to assess the cause and process of death requires knowledge about toxicokinetics, toxicodynamic, postmortem redistribution, and autopsy elements. Cocaine-related deaths occur mainly after prolonged drugs use and the presence of cocaine (COC) in fluids or tissues does not prove that death was due to COC consumption, and the interpretation of postmortem concentrations is even more complicated than attempts at making such correlations in the living. The objectives of this study were to investigate the post mortem redistribution (PMR) of COC and its metabolite benzoylecgonine (BE) in three segments of brain (frontal cortex, base nucleous, and cerebellum), vitreous humor, and blood. In additional, catecholamines and indolamines were quantified in brain in order to evaluate the usefulness of post mortem neurochemistry (PMN) in forensic toxicology. In PMR studies were quantified the COC and BE levels in three brain (BR) segments, in vitreous humor (VH), and blood (BL) by High Performance Liquid Chromatography (HPLC) with diode array detection, and for neurochemistry studies the neurotransmitters were quantified by HPLC with electrochemical detection. A homogenous distribution of COC and BE within frontal cortex, base nucleous, and cerebellum was found. The COC media concentrations were 3.09, 2.92 e 1.71µg/mL in BR, BL and VH, respectively, and the BE media concentrations were 6.12, 1.39 e 0.87 µg/mL in BL, VH, and BR, respectively. The COC concentrations in VH show high correlation with brain. The media total dopamine concentration was significant higher in COC positive group. These findings suggest that the studies of PMR and PMN by neurotransmitters levels may be useful to assess the cause and process of death.
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Harun, Norlida. "Application of molecularly imprinted solid phase extraction, enzyme-linked immunosorbent assay and liquid chromatography tandem mass spectrometry to forensic toxicology." Thesis, University of Glasgow, 2010. http://theses.gla.ac.uk/1992/.
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The rapid growth of ketamine and amphetamine misuse worldwide has led to the development of methods for the detection and analysis of ketamine and amphetamines in biological specimens. Most methods previously developed in forensic toxicology for the detection of ketamine and amphetamines used GC-MS. The present work developed alternative methods based on LC-MS/MS. Ketamine was chosen as the drug of interest because there are no data currently available on the extent of ketamine abuse in Malaysia even though a large amount of ketamine has been seized by the Malaysian Royal Police, while amphetamines are the most widely abused synthetic drugs in South East Asia including Malaysia. The study addressed some of the challenges facing the forensic toxicologist, such as the need to use new technology (LC-MS/MS) and improve sensitivity and selectivity in forensic toxicology analysis through efficient sample preparation techniques. The general requirements of method validation, including as the parameters linearity, limit of detection (LOD) and Lower Limit of Quantification (LLOQ), recovery, precision and matrix effects were observed. Three main techniques were used in the study: enzyme-linked immunosorbent assay (ELISA), liquid chromatography tandem mass spectrometry (LC-MS/MS) and molecularly imprinted polymer solid phase extraction (MISPE). MISPE is a new extraction technique in forensic toxicology applied to biological samples. Initially work was carried out on the optimization, development and validation of the Neogen® ELISA for screening ketamine and norketamine in urine. The Neogen® ketamine ELISA kit was found to be adequately sensitive and precise for ketamine screening at a cut-off concentration of 25 ng/mL. The ELISA test was shown to be highly specific to ketamine and demonstrated minimal (2.1%) cross-reactivity to its main metabolite norketamine compared to ketamine. Subsequently, an LC–MS/MS confirmation method for ketamine and norketamine in urine samples was developed and validated with application of the method to urine samples from chronic ketamine users in Malaysia. The method demonstrated good linearity, LOD, LOQ, accuracy and precision and had acceptable matrix effects. The efficiency of ELISA as a screening method at cut-off of 25 ng/ml and LC-MS/MS as a confirmation method at 2 ng/ml was evaluated. These methods complemented each other and both ELISA and LC-MS methods were 100% sensitive and specific with no false positive results for ketamine and norketamine in urine samples. The results demonstrated that a combination of these two methods can be reliably used for routine screening and confirmation of ketamine and norketamine in urine specimens. Preliminary data from this study provided information on the concentrations of ketamine and norketamine typically found in urine samples collected from individuals frequenting pubs in Malaysia. The main work in this thesis involved molecularly imprinted polymer materials which were used as sorbents in solid phase extraction (MISPE). Ketamine was used as a model substance for novel in-house synthesised MIPs as no anti-ketamine MIP have previously been reported and because the ketamine structure is suitable for the synthesis of molecularly imprinted polymers. The study was intended to improve the selectivity and sensitivity of the extraction method (MISPE) prior to LC-MS/MS analysis. Evaluation of polymer imprinting was carried out using HPLC-UV. MIP extraction and LC-MS/MS analysis were applied to the determination of ketamine and norketamine in hair samples and compared with a conventional SPE-based method. MISPE extraction was selective and sensitive with fewer matrix effects than the conventional SPE method and could also be applied to norketamine, the principal metabolite of ketamine, due to the group-selective binding nature of the MIP, but not to structurally dissimilar analytes such as PCP and tiletamine. MISPE was superior to conventional SPE for trace detection of ketamine and norketamine in hair, in terms of improved sensitivity, lower limits of detection and reduced matrix effects. In addition, the commercial product Amphetamine SupelMIPTM was evaluated for identification of amphetamines in post mortem blood coupled with LC-MS/MS analysis. This work assessed whether the MIP, sold by the manufacturer for the extraction of amphetamines in urine, could also be used for whole blood. The results demonstrated that the MIP can be used successfully for the determination of amphetamines in post mortem blood. The recoveries of five amphetamines were lower than with a comparable GC-MS method but the LODs and LLOQs of the LC-MS/MS method were better and suitable for detection of low levels amphetamines in post mortem blood. Further optimisation is needed to develop an improved protein precipitation method prior to MISPE. Liquid Chromatography Electro-Spray Ionization Mass Spectrometry (LC–ESI-MS) was used with the MISPE and SPE methods for detection and quantification of ketamine, norketamine and amphetamines in urine, whole blood and hair samples. LC-ESI-MS was found to be easy to use and could detect lower concentrations of drugs and gave reproducible results for all the methods developed in this thesis.
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Siqueira, Adriana de. "Avaliação dos efeitos tóxicos dos carbamatos: I. Modelo experimental em ratos Wistar e comparação com a intoxicação exógena intencional em gatos e cães; II. Análise de estabilidade dos compostos e dos seus efeitos nos post mortem imediato e em animais exumados." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/10/10133/tde-31082015-142508/.
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A intoxicação intencional de animais e de pessoas é uma ameaça à saúde e à segurança públicas em todo o mundo. No Brasil, os pesticidas da classe dos carbamatos aldicarbe e carbofurano são facilmente obtidos, e uma única dose letal daqueles é facilmente misturada a alimentos palatáveis e iscas. Foram analisadas as necropsias de 26 gatos e 10 cães, da rotina do Serviço de Patologia Animal da FMVZ-USP, com variados intervalos post mortem e tipos de conservação de carcaça, intoxicados pelos carbamatos aldicarbe e carbofurano, confirmados pela cromatografia de camada delgada (CCD) e cromatografia líquida de alta performance com detector de arranjo de diodos (CLAE-DAD). Foram colhidas as matrizes biológicas para histopatologia e análise toxicológica. CLAE-DAD foi utilizada para detectar o aldicarbe e seus metabólitos, aldicarbe sulfóxido e aldicarbe sulfona, e carbofurano e seu metabólito 3-hidroxicarbofurano. As análises macroscópica e histopatológica revelaram predominantemente achados congestivos e hemorrágicos, o que pode ser resultante dos efeitos tóxicos dos carbamatos e seus metabólitos. Foram feitos 2 experimentos envolvendo exposição a uma dose única de carbofurano e de aldicarbe via gavagem em ratos Wistar. No primeiro, no qual foram avaliados os efeitos no post mortem imediato, 30 animais forma separados nos seguintes grupos: aldicarbe (n=10), carbofurano (n=10) e grupo controle (n=10). Os animais foram filmados para avaliar as alterações clínicas na intoxicação aguda e, quando foram sedados, foi colhido sangue por punção cardíaca para fazer o hemograma, bioquímica sérica, colinesterase e exame toxicológico e, após a eutanásia, foi feita a necropsia e colhido material para o exame histopatológico. Em todos os animais experimentais foi possível ser feita a detecção e a quantificação do aldicarbe e do carbofurano, além das alterações microscópicas congestivas e hemorrágicas, com alterações em parâmetros hematológicos e bioquímicos. No segundo experimento, foram utilizados 30 animais, e o protocolo experimental foi idêntico ao experimento anterior, exceto que, após o óbito, os animais foram colocados em uma caixa com terra nos seguintes grupos: 1 dia, 3 dias, 5 dias, 7 dias e 10 dias, e em cada dia foram agrupados 2 animais intoxicados e 1 controle, sendo que as necropsias foram feitas nestes intervalos. Foram colhidos cérebro, pulmão, fígado e rim ao exame histopatológico e globo ocular, conteúdo gástrico, fígado e músculo esquelético ao exame toxicológico. Foram observadas as alterações tanatológicas e, em todas as matrizes analisadas, puderam ser quantificados o aldicarbe e/ou seus metabólitos aldicarbe sulfóxido e aldicarbe sulfona, bem como o carbofurano e seu metabólito 3-hidroxicarbofurano. Estes estudos mostram a importância da necropsia e da coleta de matrizes diversas ao exame toxicológico, que são complementares e cruciais na investigação de óbitos decorrentes de intoxicações por praguicidas, tanto no post mortem imediato quanto em exumaçõesThe intentional poisoning of animals and people is a threat to public health and safety worldwide. In Brazil, the carbamate pesticides aldicarb and carbofuran are easily obtained. A single lethal dose of these carbamates is easily mixed with palatable food or baits. Necropsies and histopathological examinations of 26 cats and 10 dogs poisoned by the carbamates aldicarb and carbofuran were performed in the Service of Animal Pathology of FMVZ-USP, and the poisoning was confirmed by thin layer chromatography (TLC) and high performance liquid chromatography with diode-array detector (HPLC-DAD), with variable post mortem interval and conservation of the carcass. Biological matrices were collected for histopathological and toxicological analysis. HPLC-DAD was utilised to detect aldicarb and its metabolites, aldicarb sulphoxide and aldicarb sulphone, and carbofuran and its metabolite 3-hydroxycarbofuran. Gross and histopathological evaluations showed mainly congestive and haemorrhagic findings, which may result from the toxic effects of the carbamates and their metabolites. Two experimental protocols were performed in Wistar rats by exposing them to a single oral gavage dose to the carbamates aldicarb and carbofuran. The first experiment was performed to evaluate the immediate post mortem effects of carbamates, and 30 rats were divided into three groups: aldicarb (n-=10), carbofuran (n=10) and control (n=10). The animals were filmed to evaluate the clinical signs of poisoning, and they were sedated to collect blood by heart puncture, to perform CBC, serum biochemistry, and to measure serum cholinesterase. After euthanasia, tissues were collected for histopathological evaluation. Aldicarb and carbofuran were detected and quantified in the blood of all experimental groups, and the most common histological changes observed were congestion and haemorrhage. In the second experiment, the experimental protocol was identical to the first one, but the animals were buried in a plastic box with garden soil within 5 groups of 3 animals, two exposed to the same pesticide and 1 control, as follows: day 1, day 3, day 5, day 7 and day 10. The exhumations were performed within these days (1, 3, 5, 7 and 10). We collected brain, lung, liver and kidney to examine the thanatological changes, and the eyeballs, gastric content, liver and skeletal muscle to perform the toxicological screening. Thanatological changes could be observed within and between the groups, and, in all the matrices we could detect aldicarb and its metabolites aldicarb sulphoxide and aldicarb sulphone, and carbofuran and its metabolite 3-hydroxycarbofuran. The studies have shown the importance of the necropsy and the collection of diverse matrices to the toxicological screening, because both are complementary and crucial to the investigation of deaths by pesticides poisoning, even in exhumation, since we could evaluate the thanatological changes and correlate them to the action of the pesticides in the tissues
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Lanaro, Rafael. "Determinação de paraquat e glifosato em amostras de Cannabis sativa encaminhadas para exame pericial." Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/9/9141/tde-27112008-154831/.
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No presente trabalho, foram desenvolvidos e validados dois métodos com o objetivo de determinar os herbicidas paraquat e glifosato, bem como o AMPA, principal metabólito do glifosato, em amostras de maconha apreendidas pela polícia de Campinas, São Paulo. A detecção e quantificação de herbicidas na maconha são necessárias e importantes para alertar o real risco que a droga pode oferecer aos usuários. Existem várias razões que explicam a presença de herbicidas na maconha em vários países, incluindo o Brasil. A eletroforese capilar foi utilizada para determinação dos herbicidas. Um método de detecção direta foi usado para determinar o paraquat e outro, com detecção indireta, para determinar o glifosato e AMPA. Os métodos desenvolvidos mostraram boa linearidade, precisão, exatidão e recuperação. Os dados da validação atestam que os métodos podem ser utilizados em laboratórios Forense no Brasil. Cento e trinta amostras foram analisadas, sendo que em doze amostras foram detectadas a presença de paraquat em várias concentrações e ainda três amostras forneceram resultados positivos apenas para o glifosato sendo uma delas, detectado a presença concomitante do AMPA. Os valores dos contaminantes encontrados podem representar um risco ao usuário, fazendo-se necessário novos estudos para delineamento sobre os reais efeitos que esses contaminantes podem apresentar aos usuários de Cannabis.In the present work, two methods were developed and validate, aiming to determinate the herbicides paraquat and glyphosate and his major metabolite AMPA in seizured marijuana samples by the police in Campinas, São Paulo. The determination of herbicides in confiscated samples is necessary and important to alert the real risk of marijuana can offer to the users. There are many reasons that explain the presence of herbicides in marijuana in several countries, including Brazil. Capillary electrophoresis was used to determinate the studied herbicides. A method with direct detection was used to determinate paraquat and indirect detection to determinate glyphosate and AMPA. The developed methods showed good linearity, precision, accuracy, and recovery. Therefore, it can be applied in Forensics labs in Brazil. One hundred and thirty samples were analyzed, and twelve of them result positive for paraquat in several concentrations and three samples showed positive to glyphosate and one of them, detected the presence of AMPA. The values of the contaminants found, can offer a risk to the users, making it necessary new studies to know the real effects that such contaminants can offer to the Cannabis users.
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Pereira, Carlos Victor Montefusco. "Assessment of neuronal cytotoxicity of JWH-073 and JWH-250." Master's thesis, Instituto Superior de Ciências da Saúde Egas Moniz, 2014. http://hdl.handle.net/10400.26/6715.
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Dissertação de Erasmus Mundus para obtenção do grau de mestre em Técnicas Laboratoriais ForensesSynthetic cannabinoids from marijuana herbal blends like ‘Spice’ and ‘K2’ are drawing the attention of drug of abuse organizations, including the UNODC1, the EMCCDA2 and emergency hospital all over the world. This concern rises from clinical episodes of psychotropic effects that go beyond the regular range of marijuana and THC – namely, panic attacks, psychosis, catatonia, addiction and withdrawal symptoms. Our study addressed two emergent synthetic cannabinoids (napthtoylindoles) denominated JWH-073 and JWH-250 that are currently detected on ‘Spice’-like products, in order to observe their cell toxicity profile on neuronal cells in vitro model (SH-SY5Y). Using 0.2% DMSO as negative control, MTT and LDH results revealed that within concentrations of 1, 5, 10, 25, 37.5 and 50 μM, JWH-250 is identified as ‘toxic’ in a statistically significant manner at higher concentrations. This work did not detect any statistically significant toxicity from JWH-073. This data suggests to extend these studies on new synthetic cannabinoids to neuronal cells with increased concentrations, as well as the application of assays assessing apoptosis (conditions and signalling), neuronal function and activity (as cell membrane potential assay) within differentiated cells as neurons and glia. At the same time, the evaluation of herbal mixtures of more than one cannabinoids and plant types is advisable in order to understand synergic effects.
EACEA - European Commission
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Betit, Caroline. "COMPARISON OF MULTIPLE DRUG AND METABOLITE LEVELS RECOVERED FROM SKELETONIZED REMAINS FOLLOWING STANDARD PASSIVE EXTRACTION, MICROWAVE-ASSISTED EXTRACTION AND ULTRASONIC SOLVENT EXTRACTION AND GC-MS OR UPLC-DAD." Thesis, Laurentian University of Sudbury, 2014. https://zone.biblio.laurentian.ca/dspace/handle/10219/2136.
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Lapachinske, Silvio Fernandes. "Análises físicas e químicas de comprimidos de ecstasy apreendidos no município de São Paulo." Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/9/9141/tde-17072009-114817/.
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Drug profiling, isto é, a caracterização de amostras de drogas apreendidas no sentido de estabelecer conexões entre apreensões realizadas em diferentes épocas e/ou locais a uma origem comum de produção clandestina, tem sido um objetivo dos órgãos governamentais responsáveis pela prevenção/repressão. Especificamente tratando-se de comprimidos de ecstasy, o conhecimento de suas propriedades físicas e químicas é de relevante importância para discriminar a apreensão de diferentes lotes. Nesse contexto, o presente trabalho propõe uma nova abordagem para estabelecer conexões entre apreensões de comprimidos de ecstasy, por meio da calorimetria exploratória diferencial (DSC), termogravimetria (TG) e difratometria de raios-X (DRX). Também foi realizada a caracterização física de todos os comprimidos (logotipo, coloração, massa, diâmetro e espessura), bem como a identificação/quantificação dos constituintes ativos por cromatografia em fase gasosa acoplada à espectrometria de massas (GC-MS) e o perfil de dissolução in vitro. Além disso, foi desenvolvido um método empregando a extração líquido-líquido para o isolamento da 3,4-metilenodioximetanfetamina (MDMA) dos comprimidos de ecstasy, que posteriormente foi cristalizada para cloridrato de MDMA (MDMA.HCl). Foram analisados dezessete diferentes lotes de comprimidos de ecstasy de diversos logotipos e colorações apreendidos no município de São Paulo, Brasil. Apenas um lote apresentou como única substância ativa a clorofenilpiperazina (CPP). Os outros continham apenas MDMA e o conteúdo de MDMA variou de 29 a 115-mg/comprimido. Os valores de massa dos comprimidos variaram de 143 a 341-mg, a espessura de 3,2 a 5,8-mm e o diâmetro de 7,0 a 9,5-mm. A comparação das curvas obtidas, tanto por calorimetria exploratória diferencial (DSC) como pelos difratogramas de raios-X (DRX), permitiu discriminar aqueles com perfis semelhantes, importante para identificar a origem de produção. O baixo grau de cristalinidade do MDMA.HCl de alguns comprimidos de ecstasy não impediu a caracterização por DSC e DRX. Esses resultados podem ser úteis para a aplicação no trabalho de inteligência forense.Drug profiling or the characterization of seized drug samples to link seizures made at different times and/or locations to their common clandestine origin, has long been a goal of law enforcement agencies. Considering the trafficking of ecstasy tablets, the knowledge of chemical and physical properties is of utmost importance to discriminate between different seizures. In this context this study proposed a new approach to establish links among seizures of ecstasy tablets by using differential scanning calorimetry (DSC), thermogravimetry (TG) and X-ray diffraction (XRD). Besides this characterization, physical appearance (logotype, color, weight, diameter and thickness), identification/quantification of active constituents by gas chromatography/ mass spectrometry (GC/MS) and in vitro drug dissolution assays were performed too. A method employing liquid-liquid extraction was also developed for the isolation of 3,4-methylenedioxymethamphetamine (MDMA) from ecstasy tablets and afterwards MDMA was crystallized to MDMA hydrochloride (MDMA.HCl). Seventeen different lots of various logotypes and colors of confiscated ecstasy tablets from seizures in São Paulo city, Brazil, were analyzed. Chlorophenylpiperazine (CPP) was found only as an active ingredient in one batch. The others tablets contained only MDMA and the content of MDMA varied from 29 to 115-mg/tablet. The weight values of tablets varied from 143 to 341-mg, the thickness from 3,2 to 5,8-mm and the diameter from 7,0 to 9,5-mm. DSC/TG curves and X-ray difratograms of the ecstasy tablets allowed distinguishing those with similar profile, for both techniques, which is important to identify the source of production. The low degree of MDMA.HCl crystallinity of some ecstasy tablets didnt prevent DSC and XRD characterization. These results can be useful for forensic intelligence work application.
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Paul, Richard. "New developments in analytical toxicology for the investigation of drug facilitated crime." Thesis, University of South Wales, 2007. https://pure.southwales.ac.uk/en/studentthesis/new-developments-in-analytical-toxicology-for-the-investigation-of-drug-facilitated-crime(c2b2b4e3-b8c5-471f-bf3b-daca545d4afa).html.
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Drug facilitated assault (DFA) is an increasing problem in the UK. The crime often occurs through the surreptitious administration of a drug into a victims drink, rendering the victim unable to resist the assault. The detection of these drugs in a biological specimen from the victim is one of the most challenging facets of forensic chemistry. Drug concentrations can be very low, as often only a single dose is administered, and the pharmacodynamics of commonly employed drugs further hinders the testing process. The research presented in this work shows the development of several new assays for the detection of flunitrazepam, gamma-hydroxybutyrate (GHB) and ethyl glucuronide (EtG) in a variety of biological matrices. New methods of drug testing in blood and urine are demonstrated, as well as interesting developments in the field of hair testing. Using hair to detect drug exposure allows a much wider window of detection than the more traditional matrices of blood and urine. New methods are presented in this work using gas chromatography-tandem mass spectrometry (GCMS/MS) to detect drugs in hair. Validation data is presented along with the results of authentic DFA testing. All aspects of the drug testing procedure have been evaluated, from new extraction techniques utilising water instead of solvents, to novel clean up stages involving the unique combination of SFE and SPME. Several confirmation techniques are explored including single quadrupole, triple quadrupole and ion trap mass spectrometry. In addition to developing assays for DFA cases, the versatility of this type of analytical chemistry is explored in two population studies. The first study evaluates alcohol consumption between two groups; drugs users and non drug users in medico-legal cases. There is an anecdotal belief amongst drug clinic staff that alcohol use is lower in drugs users than it is in non drug users. This study presents the first scientific confirmation of this belief through EtG (an alcohol metabolite) testing in hair of the two groups. The second study investigates whether there is a correlation between EtG and cocaethylene (a metabolite of cocaine only produced in the presence of alcohol) in cocaine users. Results f this study suggest that there is no positive correlation between the two compounds. The research presented in this thesis aims to further the analytical science surrounding FA investigation and provide accurate, sensitive and reliable methodology for drug esting in blood, urine and hair.
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Costa, José Luiz da. "Determinação de 3,4-metilenodioximetanfetamina (MDMA - Ecstasy), 3,4-metilenodioxietilanfetamina (MDEA - Eve) e 3,4-metilenodioxianfetamina (MDA) em fluidos biológicos por cromatografia líquida de alta eficiência: aspecto forense." Universidade de São Paulo, 2004. http://www.teses.usp.br/teses/disponiveis/9/9141/tde-11032005-190039/.
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Em todo o mundo é crescente o uso drogas de abuso sintéticas conhecidas com designer drugs. Os principais representantes desta classe são o Ecstasy ou 3,4-metilenodioximetanfetamina (MDMA) e o Eve ou 3,4-metilenodioxietilanfetamina (MDEA), substâncias com efeitos estimulantes e alucinógenos. No Brasil é crescente sua divulgação pela mídia e o uso recreacional tem sido constatado em vários pacientes que buscam tratamento nas clínicas para dependentes. O presente trabalho constitui validação de metodologia analítica para o diagnóstico laboratorial do uso de MDMA, MDEA e seu produto de biotransformação, o 3,4-metilenodioxianfetamina (MDA), em sangue total e urina, por cromatografia líquida de alta eficiência com detecção por fluorescência. Os métodos desenvolvidos mostraram boa linearidade, precisão, exatidão, rendimento e capacidade de detectar os analitos mesmos quando presentes em baixas concentrações, o que permite sua aplicação na verificação da intoxicação aguda quanto no uso recreacional destas drogas de abuso.There is a worldwide increase in the use of the synthetic drugs of abuse known as designer drugs. The main representatives of this class are Ecstasy or 3,4-methylenodioxymethamphetamine (MDMA) and Eve or 3,4- methylenodioxyethylamphetamine (MDEA), substances with stimulant and hallucinogenic effects. In Brazil media coverage of them is on the increase and their recreational is in evidence by the growing numbers of patients who seek treatment at drug treatment centers. This paper validates the analytical methodology for the laboratory diagnosis of the use of MDMA, MDEA and their product of biotransformation, 3,4-methylenodioxyamphetamine (MDA), in whole blood and urine by high performance liquid chromatography with fluorescence. The developed methods showed good linearity, precision, accuracy, yield and capacity to detect analytes even when present in low concentrations, which enables its application in cases high intoxication as well as in cases of the recreational use of these drugs of abuse.
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Eckberg, Melanie N. "Forensic Toxicological Screening and Confirmation of 800+ Novel Psychoactive Substances by LC-QTOF-MS and 2D-LC Analysis." FIU Digital Commons, 2018. https://digitalcommons.fiu.edu/etd/3923.
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Novel psychoactive substances (NPS) represent a great challenge to toxicologists due to the ability of illicit drug manufacturers to alter NPS chemical structures quickly and with ease to circumvent legislation regulating their use. Each time a new structure is introduced, there is a possibility that it has not been previously recorded in law enforcement or scientific databases. Many toxicology laboratories use targeted analytical methods that rely on libraries of known compounds to identify drugs in samples. However, these libraries do not include large numbers of NPS which could result in non-identification or detection.
High-resolution mass spectrometry (HRMS) has been suggested as a method for screening a wide variety of analytes due to its higher sensitivity and mass accuracy as compared to some other forms of mass spectrometry. This technique can generate characteristic MS/MS spectral data for use in compound identification. The main goal of this research was to create a high-resolution mass spectrometry (HRMS) library of NPS and metabolites, as well as validate a method for screening and confirmation of these substances. The study consisted of three main tasks which included; the development of a large high-resolution MS/MS spectral library and database, validation of a method for screening and confirmation of over 800 NPS and metabolites, and screening of blind-spiked and authentic urine specimens to determine real-world applicability of the HRMS library and method.
During validation, several isomeric and structurally related NPS were observed which could not be adequately separated using traditional LC methods. A fourth task was therefore added to investigate improved separation using two-dimensional liquid chromatography (2D-LC). Increased resolving power is achieved in 2D-LC through the coupling of multiple orthogonal separation systems. Ultimately, an on-line, comprehensive method was developed using orthogonal reversed-phase columns in each dimension (RP x RP) for improved separation of co-eluting and isomeric synthetic cannabinoids.
This work can aid laboratories in the identification of NPS through the use of a validated LC-QTOF-MS method for screening and confirmation and HRMS spectral library. In instances where isomeric and structurally related NPS are not sufficiently separated, RP x RP methods can be explored.
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Leite, Flávia Pine. "Determinação de club dugs em sangue total por cromatografia líquida acoplada a espectrometria de massas com analisador híbrido quadrupolo-tempo de voo (LC-QTOF-MS)." Universidade de São Paulo, 2018. http://www.teses.usp.br/teses/disponiveis/9/9141/tde-11062018-110009/.
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As chamadas club drugs compreendem um vasto grupo de substâncias frequentemente utilizadas em bares, festas e raves, com a finalidade de intensificar o contato social e a estimulação sensorial. Englobam desde substâncias sintéticas comumente conhecidas, como a anfetamina, a metanfetamina, o MDMA, até moléculas de surgimento mais recente, denominadas novas substâncias psicoativas. Isoladas ou associadas a outras drogas, é possível que sejam causa de morte per se, ou que predisponham o usuário a envolver-se em situações potencialmente fatais, sendo necessário que os órgãos de Perícia Criminal (Institutos Médico Legais e Institutos de Criminalística) estejam aptos a detectar e quantificar essas substâncias em amostras biológicas. O presente trabalho teve como objetivo desenvolver um método analítico para identificação e quantificação de club drugs em sangue total, utilizando cromatografia líquida acoplada a espectrometria de massas com analisador híbrido quadrupolotempo de voo (LC-QTOF). Após o desenvolvimento do método, este foi validado utilizando as diretrizes do guia de validação do Scientific Working Group for Forensic Toxicology (SWGTOX), sendo analisados de linearidade, limite de detecção, limite de quantificação, efeito matriz, precisão intradia, precisão interdia, exatidão e integridade de diluição, além de recuperação e eficiência do processo. O método desenvolvido compreendeu a determinação de MDA, MDMA, 2C-B, DOB, cetamina, mCPP, cocaína e cocaetileno. Amostras provenientes de casos reais de morte não natural, oriundas do Instituto Médico Legal Aristoclides Teixeira de Goiânia - GO foram analisadas pelo método desenvolvido. 56 casos foram selecionados, em sua maioria com histórico de morte por projétil de arma de fogo e acidente de transito. Das 56 amostras analisadas, 28,5% (n=16) foram positivas para cocaína e/ou cocaetileno. As demais substâncias pesquisadas não foram encontradas nas amostras.Club drugs are a large group of substances consumed in pubs, parties and raves, aiming to intensify social contact and sensorial stimulation. The term comprises largely known substances such as amphetamine, methamphetamine, 3,4-methylenodioxymethamphetamine (MDMA), as well as so-called new psychoactive substances, which are synthetic drugs recently developed or recently introduced in drug market. Club drugs can be taken alone, combined with each other or, most frequently, with alcohol or other commonly abused drugs such as cocaine. In any of these situations, club drugs can possibly be the cause of death or potentialize the involvement of the user with crime and potentially fatal behavior. Thus, official organisms in charge of criminal investigation must be capable of identifying and quantifying these substances in biological samples. The present work aimed the development of an analytical method to identify and quantify club drugs in whole blood, using liquid chromatography - mass spectrometry with hybrid analyzer quadrupole - time of flight (LC-QTOF). After analytical development, the method was validated according to do Scientific Working Group for Forensic Toxicology (SWGTOX) guidelines, evaluating linearity, limit of detection, limit of quantification, matrix effect, precision, intermediate precision, bias and dilution integrity, besides recovery and process efficiency. The developed method comprised MDA, MDMA, 2C-B, DOB, ketamine, mCPP, cocaine and cocaethylene determination. Real samples related to non-natural deaths were collected at Institute of the Legal Medicine Aristoclides Teixeira, Goiânia, Goiás, Brazil, and analyzed by the developed method. 56 cases were selected, most of them related to fire gun injury and traffic events, 28,5% (n=16) of them being positive for cocaine and/or cocaethylene. None of the other drugs comprised in the analysis were detected in these samples.
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Gilbertson, Michael. "Injury to health : a forensic audit of the Great Lakes Water Quality Agreement (1972-2005) with special reference to congenital Minamata disease." Thesis, University of Stirling, 2006. http://hdl.handle.net/1893/249.
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The objective of this research was to examine whether the United States and Canada have successfully implemented their Great Lakes Water Quality Agreement and to identify the factors determining the continuation of any injury to human health from pollution of the boundary waters. The Agreement was first negotiated in 1972 as part of the legitimation of the social unrest of the 1960s and gave special responsibilities to the International Joint Commission to advise the Parties of problems of water quality. It has been subject to periodic review and occasional renegotiation and amendment. Specifically, the Agreement was renegotiated in 1978 to address the health effects from the imperceptible exposures to persistent toxic substances. Though extensive scientific evidence of continuing injury to health from persistent toxic substances has been available, there has been a consistent pattern of deliberate failure by the authorities to report the injury and to implement many of the remedial provisions contained in the Agreement. The thesis claims that the failure of the International Joint Commission to advise the Parties of the new information about the injury to health and the failure of the Parties to act upon the information when it was obtained from other sources constituted dereliction of duty. While synthesis of the science linking the pollutant-induced injury to specific causal agents was necessary to provide an empirical measure of the failure to implement the Agreement, consideration of the social, economic and political aspects was needed to provide a sufficient explanation for the failure of the International Joint Commission to inform and of the authorities to act. There have been active attempts to use diversionary reframing of the Agreement, based on a multi-causal ecosystem theory proposed by fisheries ecologists, to attenuate the risk message and transform the Great Lakes Water Quality Agreement into a more inclusive and less focused agreement on restoring ecosystem integrity. This has been welcomed by industry and governments as a means to remove the focus from addressing the unresolved dangers of persistent toxic substances through costly remedial actions. The International Joint Commission undermined its credibility when it recommended ‘sunsetting’ the use of chlorine in chemical manufacturing. The Parties failed to use a precautionary approach to prevent the commercial introduction of new persistent toxic substances, such as the brominated flame retardants. Since the 1980s, the economic politics of the two nations have been profoundly influenced by neo-liberalism and one of the consequences has been the removal of environmental health as a priority from the respective political agenda. Advisory bodies seem to have been captured not only by the prevailing neo-liberalism but also by corporate interests and these factors seem to underlie the reluctance to report the injury to health from exposures to persistent toxic substances. Though there were many different health endpoints affected by exposures to water pollutants in the Great Lakes, the thesis concentrated on the evidence of neuro-teratogenic effects. The adequacy of the implementation of the Agreement during the past thirty-three years was tested by using Health Canada data on cerebral palsy hospitalisation to evaluate whether there were indications of previously undetected outbreaks of congenital Minamata disease in human populations in Canadian Great Lakes communities potentially exposed to methyl mercury from natural sources or from historic industrial uses of mercury. The uncertainties in the apparent association that was found were reduced by the application of Hill’s guidelines. While these findings indicated both the need for further multi-disciplinary research to locate and diagnose the victims and for a precautionary approach to the consumption of Great Lakes fish, they also indicated that, for more than three decades, health authorities have not diligently implemented the Agreement. The inclusion of the social, economic and political considerations in the forensic audit has revealed the dangers inherent in any renegotiation of the Great Lakes Water Quality Agreement.
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Carlier, Jérémy. "Implication médico-légale des toxiques d'origine végétale : approche analytique." Thesis, Lyon 1, 2014. http://www.theses.fr/2014LYO10221/document.
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Les intoxications ayant pour cause la prise de toxiques végétaux sont relativement fréquentes. Ces intoxications font suites à une ingestion accidentelle ou volontaire (aliments contaminés, préparations à but « thérapeutique », acte suicidaire, .). Le nombre de ces intoxications est sous-estimé car les signes cliniques sont souvent non spécifiques et les médecins méconnaissent la dangerosité des composés présents et l'incidence des intoxications par les plantes. La sous-estimation du nombre d'intoxications est également liée au manque de méthodes analytiques développées spécifiquement pour la détermination de ces toxines. Enfin de nombreuses molécules restent, à l'heure actuelle, indétectables avec les outils analytiques disponibles. L'objectif de cette thèse était de mettre en lumière l'implication des plantes en toxicologie médico- légale et de proposer des méthodes analytiques pour des composés qui, jusqu'alors, n'étaient pas disponibles. Nous avons développé un screening en CLHP-SM/SM et en CLHP-HRSM/SM pour l'analyse du plus grand nombre de phytotoxines simultanément dans des prélèvements biologiques. Ces méthodes ont été éprouvées par plusieurs cas réels d'intoxication. Nous avons développé la première méthode d'analyse toxicologique de l'hypoglycine A, de l'atractyloside et du carboxyatractyloside applicable en médecine légale. Nous avons enfin approfondi la connaissance des principes toxiques du faux manguier. L'ensemble de ce travail confirme l'importance de l'analyse toxicologique des phytotoxines en médecine légale. Les travaux réalisés ont permis d'approfondir les connaissances sur les toxiques végétaux et de combler certaines lacunes analytiquesPlant poisonings are relatively common. They are caused by accidental or voluntary ingestion (contaminated food, "therapeutic" preparations, suicide attempts.). The number of such poisonings is underestimated, since the clinical signs are often non- specific and doctors are unaware of the incidence of plant poisonings or of the dangerous nature of the compounds present. The lack of analytical methods developed specifically to determine these toxins is another factor in the underestimation of the number of plant poisonings. Furthermore, many molecules are still undetectable with the analytical tools currently available. The aim of this thesis was to highlight the part played by plants in forensic toxicology, and to propose analytical methods for compounds, which up to now had not been available. We have developed a screening method in HPLC-MS/MS and HPLC-HRMS/MS for analysing the highest number of phytotoxins simultaneously in biological samples. The methods were tested on several real poisoning cases. We developed the first toxicological analysis method applicable in forensic medicine for hypoglycin A, atractyloside and carboxyatractyloside. We then deepened our knowledge of the toxic principles of the sea mango. This work, as a whole, confirms the importance of toxicological analysis of phytotoxins in forensic medicine. The work carried out enabled us to improve our knowledge of plant poisons and to fill some analytical gaps