Academic literature on the topic 'Bumetanida'

Uptakes of 22Na, 36Cl, and 86Rb into isolated bovine tracheal epithelial cells were measured in the presence and absence of 10 microM bumetanide. Preincubation with ouabain (0.5 mM) did not alter initial rates of Na and Cl uptakes but prolonged from 0.5 or less to 2 min the period in which Na uptake is linear with time. Initial rates of bumetanide-inhibitable Na and Cl uptakes (influxes), measured for 2 min in identical solutions, were similar in magnitude (bumetanide-sensitive Cl influx/bumetanide-sensitive Na influx = 1.2). Omission of K did not affect bumetanide-sensitive Na or Cl influx. Cl influx was not affected by 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid. Amiloride (0.1 mM) partially inhibited the bumetanide-insensitive Na influx but had no effect on the bumetanide-sensitive Na influx. Rb influx was not affected by bumetanide but was markedly reduced by ouabain and slightly reduced by Ba, the combination being additive. Half-maximally inhibitory concentration values for inhibition of Cl influx by 4 sulfamoylbenzoic acid derivatives were as follows (in mumol/l): 0.125 benzmetanide; 0.64 bumetanide; 16 piretanide; and 26 furosemide. Affinities of Na and Cl for the bumetanide-inhibitable cotransport process were determined by measuring bumetanide-sensitive Cl influx at varying [Na] and bumetanide-sensitive Na influx at varying [Cl]. Both plots were hyperbolic, and the K0.5 values for Na and Cl were 4.1 and 53.9 mM, respectively. Bumetanide-inhibitable Cl influx was not altered by secretory stimuli (epinephrine, A23187) but was more than doubled by osmotic shrinkage (200 mM mannitol or sucrose).(ABSTRACT TRUNCATED AT 250 WORDS)

Rb+ uptake into LLC-PK1/Cl 4 cells can be subdivided into three components: 1) ouabain-sensitive uptake, 2) bumetanide-sensitive uptake, and 3) ouabain- and bumetanide-insensitive uptake. Exposure of cells to near-UV light in the presence of low concentrations of bumetanide produces a specific, irreversible inhibition of the bumetanide-sensitive uptake component, while not affecting the other two uptake components. Irreversible inhibition of bumetanide-sensitive transport is observed when measuring either cellular uptake or efflux and also when measuring 86Rb+ uptake into membrane vesicles. The irreversible inhibition is both concentration and time dependent and is blocked under conditions where the interaction of bumetanide with the Na+-K+-Cl- cotransporter is disturbed. We conclude that bumetanide, at low concentrations, can specifically and irreversibly inhibit the Na+-K+-Cl- cotransporter of LLC-PK1/Cl 4 cells. We suggest that this irreversible inhibition is the result of the photoactivation of an ether linkage in the bumetanide molecule, leading to a covalent binding of bumetanide to the Na+-K+-Cl- cotransporter.

The uptake of [3H]bumetanide was studied in isolated skate hepatocytes in an albumin-free elasmobranch Ringer solution and compared with the uptake of bile acids in the presence of other cholephilic organic anions. [3H]bumetanide uptake was energy dependent, temperature sensitive, and exhibited saturation kinetics. In contrast to taurocholate and cholate, which are transported only by Na(+)-independent mechanisms, removal of Na+ reduced the maximal uptake rate (Vmax) for bumetanide from 404 +/- 80 to 230 +/- 47 pmol.mg-1 x min-1 without a change in the apparent Michaelis constant (Km). The apparent Km for the Na(+)-dependent portion of bumetanide uptake was 58 +/- 24 microM, and Vmax was 151 +/- 38 pmol.min-1 x mg-1. Taurocholate (100 and 200 microM) inhibited Na(+)-independent bumetanide transport competitively but was a noncompetitive inhibitor for Na(+)-dependent bumetanide uptake. Furosemide (100 microM) and two bumetanide analogues, PF-3034 (500 microM) and PF-2203 (500 microM), preferentially inhibited the Na(+)-dependent bumetanide uptake system, whereas cholate (100 microM) and probenecid (100 microM) preferentially inhibited Na(+)-independent bumetanide transport. The sulfhydryl (SH) reagents N-ethylmaleimide, 2,2'-dithio-bis(5-nitropyridine), and p-chloromercuribenzenesulfonic acid (PCMBS) inhibited both bile acid and bumetanide uptake. Dithiothreitol (500 microM) completely reversed the PCMBS-induced inhibition of bumetanide uptake. These results indicate that bumetanide is transported into hepatocytes of the small skate, Raja erinacea, by both Na(+)-dependent and Na(+)-independent mechanisms; the latter is shared by bile acids and probably sulfobromophthalein and other organic anions. Their uptake requires free SH groups.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Neste trabalho foram desenvolvidos três métodos ambientalmente amigáveis para quantificar bumetanida. O primeiro método desenvolvido foi o de espectroscopia de reflectância difusa utilizando spot test. O método é baseado na reação entre bumetanida e o reagente cromogênico p-dimetilaminocinamaldeído (p-DAC - 3,4 x 10-2 mol L-1) em meio ácido (HCl - 2,1 x 10-1 mol L-1) sobre a superfície de um papel de filtro, produzindo um complexo colorido (?máx = 525 nm) estável. Para a reação apenas 20 æL de cada solução foi utilizada, sendo um procedimento limpo, pois gera pouco resíduo ao meio ambiente. A faixa de trabalho estudada variou entre 1,37 x 10-4 a 1,37 x 10-3 mol L-1 (50-500 ppm). Os limites de detecção (LOD) e de quantificação (LOQ) calculados foram 3,98 x 10-5 e 1,33 x 10-4 mol L-1 respectivamente. O segundo método foi o de análise por injeção em fluxo com detecção espectrofotométrica utilizando o sistema de adição de reagente por confluência. O método também se baseia na reação entre bumetanida e p-DAC supracitada, com o diferencial de usar de meio micelar (Dodecil Sulfato de Sódio (SDS)), o que acarretou um aumento na sensibilidade de cerca de 4,75 vezes. O reagente (p-DAC 5,6 x 10-3 mol L-1 preparado em HCl 6,2 x 10-2 mol L-1) é adicionado no percurso analítico através de uma confluência, onde reage com 918 æL de solução contendo o analito em uma bobina reacionária de 163 cm . Ambas as soluções foram transportadas por uma solução de SDS 8,0 x 10-3 mol L-1. A faixa de trabalho foi de 1,37 x 10-6 a 2,77 x 10-5 mol L-1 (0,5-10 ppm). Os limites de detecção (LOD) e de quantificação (LOQ) calculados foram 3,07 x 10-7 e 1,03 x 10-6 mol L-1 respectivamente. A freqüência analítica obtida foi de 69 análises por hora. O terceiro e último método desenvolvido foi o de análise por injeção...
In this work were developed three environmentally friendly analytical methods for quantification of bumetanide. The first method developed was diffuse reflectance spectroscopy using spot test analysis. The method is based on the reaction between bumetanide and colored reagent p-dimethylaminocinnamaldeyde (p-DAC - 3.4 x 10-2 mol L-1) in acid medium (HCl - 2.1 x 10-1 mol L-1) on the surface of filter paper, yielding a stable colored product (? = 525 nm). For the reaction only 20 æL of reagent was applied, it's a clear procedure, yielding a little quantity of residues. The linear range was 1.37 x 10-4 to 1.37 x 10-3 mol L-1 (50 - 500 æg mL-1). The limits of detection (LOD) and quantification (LOQ) estimated were 3.98 x 10-5 and 1.33 x 10-4 mol L-1 respectively. The second method was flow injection analysis using spectrophotometric determination using the system with continuous reagent addition. The method is based on the reaction between bumetanide and p-DAC above mentionated, but using a micellar medium (Sodium Dodecyl Sulfate (SDS)), allowing up to 4.75 fold increase in sensitivity. The reagent (p-DAC 5.6 x 10-3 mol L-1 in HCl 6.2 x 10-2 mol L-1) is added on the analytical course using a confluence, where it reacts with 918 æL of sample solution in reaction coil of 163 cm. The solutions were carried by a SDS solution 8.0 x 10-3 mol L-1 The linear range was 1.37 x 10-6 to 2.77 x 10-5 mol L-1 (0.5 -10 æg mL-1). The limits of detection LOD) and quantification (LOQ) estimated were 3.07 x 10-7 e 1.03 x 10-6 mol L-1 respectively. The average sample rate of 69 determinations per hour. The last method developed was flow injection analysis exploiting merging zones. In this case the reagent isn't added continously it has fixed volume on the reaction... (Complete abstract, click electronic access below)

Resumo: Neste trabalho foram desenvolvidos três métodos ambientalmente amigáveis para quantificar bumetanida. O primeiro método desenvolvido foi o de espectroscopia de reflectância difusa utilizando spot test. O método é baseado na reação entre bumetanida e o reagente cromogênico p-dimetilaminocinamaldeído (p-DAC - 3,4 x 10-2 mol L-1) em meio ácido (HCl - 2,1 x 10-1 mol L-1) sobre a superfície de um papel de filtro, produzindo um complexo colorido (?máx = 525 nm) estável. Para a reação apenas 20 æL de cada solução foi utilizada, sendo um procedimento limpo, pois gera pouco resíduo ao meio ambiente. A faixa de trabalho estudada variou entre 1,37 x 10-4 a 1,37 x 10-3 mol L-1 (50-500 ppm). Os limites de detecção (LOD) e de quantificação (LOQ) calculados foram 3,98 x 10-5 e 1,33 x 10-4 mol L-1 respectivamente. O segundo método foi o de análise por injeção em fluxo com detecção espectrofotométrica utilizando o sistema de adição de reagente por confluência. O método também se baseia na reação entre bumetanida e p-DAC supracitada, com o diferencial de usar de meio micelar (Dodecil Sulfato de Sódio (SDS)), o que acarretou um aumento na sensibilidade de cerca de 4,75 vezes. O reagente (p-DAC 5,6 x 10-3 mol L-1 preparado em HCl 6,2 x 10-2 mol L-1) é adicionado no percurso analítico através de uma confluência, onde reage com 918 æL de solução contendo o analito em uma bobina reacionária de 163 cm . Ambas as soluções foram transportadas por uma solução de SDS 8,0 x 10-3 mol L-1. A faixa de trabalho foi de 1,37 x 10-6 a 2,77 x 10-5 mol L-1 (0,5-10 ppm). Os limites de detecção (LOD) e de quantificação (LOQ) calculados foram 3,07 x 10-7 e 1,03 x 10-6 mol L-1 respectivamente. A freqüência analítica obtida foi de 69 análises por hora. O terceiro e último método desenvolvido foi o de análise por injeção... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: In this work were developed three environmentally friendly analytical methods for quantification of bumetanide. The first method developed was diffuse reflectance spectroscopy using spot test analysis. The method is based on the reaction between bumetanide and colored reagent p-dimethylaminocinnamaldeyde (p-DAC - 3.4 x 10-2 mol L-1) in acid medium (HCl - 2.1 x 10-1 mol L-1) on the surface of filter paper, yielding a stable colored product (? = 525 nm). For the reaction only 20 æL of reagent was applied, it's a clear procedure, yielding a little quantity of residues. The linear range was 1.37 x 10-4 to 1.37 x 10-3 mol L-1 (50 - 500 æg mL-1). The limits of detection (LOD) and quantification (LOQ) estimated were 3.98 x 10-5 and 1.33 x 10-4 mol L-1 respectively. The second method was flow injection analysis using spectrophotometric determination using the system with continuous reagent addition. The method is based on the reaction between bumetanide and p-DAC above mentionated, but using a micellar medium (Sodium Dodecyl Sulfate (SDS)), allowing up to 4.75 fold increase in sensitivity. The reagent (p-DAC 5.6 x 10-3 mol L-1 in HCl 6.2 x 10-2 mol L-1) is added on the analytical course using a confluence, where it reacts with 918 æL of sample solution in reaction coil of 163 cm. The solutions were carried by a SDS solution 8.0 x 10-3 mol L-1 The linear range was 1.37 x 10-6 to 2.77 x 10-5 mol L-1 (0.5 -10 æg mL-1). The limits of detection LOD) and quantification (LOQ) estimated were 3.07 x 10-7 e 1.03 x 10-6 mol L-1 respectively. The average sample rate of 69 determinations per hour. The last method developed was flow injection analysis exploiting merging zones. In this case the reagent isn't added continously it has fixed volume on the reaction... (Complete abstract, click electronic access below)
Orientador: Leonardo Pezza
Coorientador: Helena Redigolo Pezza
Banca: Massao Ionashiro
Banca: Matthieu Tubino
Mestre

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O presente trabalho está baseado na construção de sensores biomiméticos para determinação sensível e seletiva dos diuréticos: bumetanida (BMT) e hidroclorotiazida (HCTZ). Para isto, eletrodos à base de pasta de carbono foram modificados com complexos, os quais são potenciais catalisadores biomiméticos das enzimas P450, que catalisam um grande número de reações incluindo os fármacos. Os complexos que apresentaram perfil biomimético e melhores resultados na determinação voltamétrica e amperométrica da bumetanida e hidroclorotiziada, respectivamente foram 1,2,3,4,8,9,10,11,15,16,17,18,22,23,24,25-hexadecafluoro 29-H, 31-H-ftalocianinacobre (II) [CuPc] e hemina. As condições experimentais para o desenvolvimento das metodologias propostas foram otimizadas com auxílio de planejamento de experimentos multivariados. O sensor construído para determinação do diurético bumetanida apresentou as melhores respostas em solução tampão Britton-Robinson 0,15 mol L-1 pH 7,0 e 15% m/m do complexo [CuPc], usando a voltametria de onda quadrada a 60 Hz, 100 mV de amplitude e 6 mV de incremento de potencial (Δps). Com os parâmetros otimizados, o sensor apresentou limites de detecção e de quantificação de 0,27 e 0,9 μmol L-1, respectivamente. Os melhores resultados obtidos para o sensor desenvolvido para a hidroclorotiazida foram em solução fosfato 0,10 mol L-1 pH 8,5 e 14% m/m de hemina usando a amperometria em 800 mV, e os limites de detecção e de quantificação de 8,2 e 27 μmol L-1, respectivamente. Avaliou-se também a biomimeticidade do sensor, explorando o perfil hiperbólico da resposta nos sensores, velocidade de varredura e estudo de interferentes. Os sensores foram satisfatoriamente usados nas análises em amostras de interesse farmacêutico e biológico, assim se apresentam com alternativas vantajosas em relação a outros métodos disponíveis, pois apresentam baixo custo...
This work is based on the construction of biomimetic sensors for sensitive and selective determination of diuretics for bumetanide (BMT) and hydrochlorothiazide (HCTZ). Carbon paste-based electrodes were modified with complexes, which are potential biomimetic catalysts of P450 enzymes, that catalyze a number of reactions including pharmaceuticals. The complexes Copper (II) 1,2,3,4,8,9,10, 11,15,16,17,18,22,23,24,25-hexadecafluoro-29-H,31-H-phthalocyanine [CuPc] and Hemin showed biomimetic profile and better results for amperometric and voltammetric determination of bumetanide and hidroclorotiziada, respectively. The experimental conditions for the proposed methodologies development have been optimized with the help of design of multivariate experiments. The sensor built to determine the diuretic bumetanide presented the best responses in Britton-Robinson buffer 0.15 mol L-1 pH 7.0 and 15 % (m/m) of the complex [CuPc], using the square wave voltammetry with 60 Hz, amplitude of potential of 100 mV and step potencial of 6 mV. With the optimized parameters the sensor showed limits of detection and quantification of 0.27 and 0.9 μmol L-1,respectively. The best results for the sensor have been developed for hydrochlorothiazide phosphate solution 0.10 mol L-1 pH 8.5 and 14 % (m/m) of the hemin, using the amperometry at 800 mV, limits of detection and quantification of 8.2 and 27 μmol L-1, respectively. Studies conducted for elucidation of sensor biomimetic behavior, such as evaluation of scan rate influence using cyclic voltammetry, exploration of hyperbolic profile of the sensor response, interference and selectivity studies. In a complementary, a molecular imprinting polymer, known as MIP, was developed for bumetanide. The MIPs were synthesized by bulk polymerization. Studies were based on the results obtained from the computer simulation where monomer of high structural affinity, acrylonitrile...

Orientador: Maria Del Pilar Taboada Sotomayor
Banca: Fabíola Manhas Verbi Pereira
Banca: Gustavo Troiano Feliciano
Banca: Luiz Henrique Mazo
Banca: Marcos Roberto de Vasconcelos Lanza
Resumo: O presente trabalho está baseado na construção de sensores biomiméticos para determinação sensível e seletiva dos diuréticos: bumetanida (BMT) e hidroclorotiazida (HCTZ). Para isto, eletrodos à base de pasta de carbono foram modificados com complexos, os quais são potenciais catalisadores biomiméticos das enzimas P450, que catalisam um grande número de reações incluindo os fármacos. Os complexos que apresentaram perfil biomimético e melhores resultados na determinação voltamétrica e amperométrica da bumetanida e hidroclorotiziada, respectivamente foram 1,2,3,4,8,9,10,11,15,16,17,18,22,23,24,25-hexadecafluoro 29-H, 31-H-ftalocianinacobre (II) [CuPc] e hemina. As condições experimentais para o desenvolvimento das metodologias propostas foram otimizadas com auxílio de planejamento de experimentos multivariados. O sensor construído para determinação do diurético bumetanida apresentou as melhores respostas em solução tampão Britton-Robinson 0,15 mol L-1 pH 7,0 e 15% m/m do complexo [CuPc], usando a voltametria de onda quadrada a 60 Hz, 100 mV de amplitude e 6 mV de incremento de potencial (Δps). Com os parâmetros otimizados, o sensor apresentou limites de detecção e de quantificação de 0,27 e 0,9 μmol L-1, respectivamente. Os melhores resultados obtidos para o sensor desenvolvido para a hidroclorotiazida foram em solução fosfato 0,10 mol L-1 pH 8,5 e 14% m/m de hemina usando a amperometria em 800 mV, e os limites de detecção e de quantificação de 8,2 e 27 μmol L-1, respectivamente. Avaliou-se também a biomimeticidade do sensor, explorando o perfil hiperbólico da resposta nos sensores, velocidade de varredura e estudo de interferentes. Os sensores foram satisfatoriamente usados nas análises em amostras de interesse farmacêutico e biológico, assim se apresentam com alternativas vantajosas em relação a outros métodos disponíveis, pois apresentam baixo custo...
Abstract: This work is based on the construction of biomimetic sensors for sensitive and selective determination of diuretics for bumetanide (BMT) and hydrochlorothiazide (HCTZ). Carbon paste-based electrodes were modified with complexes, which are potential biomimetic catalysts of P450 enzymes, that catalyze a number of reactions including pharmaceuticals. The complexes Copper (II) 1,2,3,4,8,9,10, 11,15,16,17,18,22,23,24,25-hexadecafluoro-29-H,31-H-phthalocyanine [CuPc] and Hemin showed biomimetic profile and better results for amperometric and voltammetric determination of bumetanide and hidroclorotiziada, respectively. The experimental conditions for the proposed methodologies development have been optimized with the help of design of multivariate experiments. The sensor built to determine the diuretic bumetanide presented the best responses in Britton-Robinson buffer 0.15 mol L-1 pH 7.0 and 15 % (m/m) of the complex [CuPc], using the square wave voltammetry with 60 Hz, amplitude of potential of 100 mV and step potencial of 6 mV. With the optimized parameters the sensor showed limits of detection and quantification of 0.27 and 0.9 μmol L-1,respectively. The best results for the sensor have been developed for hydrochlorothiazide phosphate solution 0.10 mol L-1 pH 8.5 and 14 % (m/m) of the hemin, using the amperometry at 800 mV, limits of detection and quantification of 8.2 and 27 μmol L-1, respectively. Studies conducted for elucidation of sensor biomimetic behavior, such as evaluation of scan rate influence using cyclic voltammetry, exploration of hyperbolic profile of the sensor response, interference and selectivity studies. In a complementary, a molecular imprinting polymer, known as MIP, was developed for bumetanide. The MIPs were synthesized by bulk polymerization. Studies were based on the results obtained from the computer simulation where monomer of high structural affinity, acrylonitrile...
Doutor

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Este trabalho descreve o desenvolvimento de métodos analíticos para a determinação quantitativa de furosemida e bumetanida em amostras de urina utilizando espectroscopia por reflectância difusa (para a furosemida) e por imagem por scanner com quantificação através do histograma de cores utilizando o padrão RGB (para ambas). Envolve também o desenvolvimento de um método quantitativo para a detecção de chumbo em resíduos de armas de fogo (GSR) nas mãos de atiradores utilizando membranas de celulose bacteriana como substrato de coleta, visando o descobrimento do tempo de disparo. Também foi realizada a quantificação de chumbo em amostras de tintura para cabelos utilizando método previamente desenvolvido, visando detecção da adulteração destes produtos e controle de qualidade. Estuda também a potencialidade do uso das membranas de celulose bacteriana para a coleta de impressões digitais. Os métodos desenvolvidos consistem na reação da furosemida (FUR) com o regente cromogênico paradimetilaminocinamaldeído (p-DAC) 0,70% e ácido clorídrico (HCl) 1,72 mol L-1 em papel de filtro qualitativo com barreiras hidrofóbicas, com detecção espectrofotométrica e por histograma de cores; na reação do íon chumbo(II) (Pb2+) com rodizonato de sódio (ROD) 0,16% em meio micelar de dodecil sulfato de sódio (SDS) 5 mmol L-1 em membranas de celulose bacterianas, com detecção espectrofotométrica e por microscopia eletrônica de varredura (MEV); na reação de bumetanida (BMT) com o reagente p-DAC 0,6% e HCl 0,26 mol L-1 em papel de filtro qualitativo com barreiras hidrofóbicas, com detecção por histograma de cores e na coleta de impressões digitais utilizando membrana de celulose bacteriana impregnadas com ninidrina, nitrato de prata ou óxido de zinco, dos quais o nitrato de prata e a ninidrina atuaram como agentes de coleta razoáveis. Todas as concentrações foram otimizadas por planejamentos quimiométricos. As reações foram realizadas na forma de spot test, envolvendo a formação de um produto colorido em 545 nm para o chumbo, em 585 nm para a furosemida e 520 nm para a bumetanida. As curvas analíticas foram contruídas a partir de soluções padrões dos respectivos analitos. Os métodos desenvolvidos para a bumetanida e para a furosemida foram aplicados em amostras de urina sintética e natural fortificadas e os resultados obtidos foram comparados estatisticamente com métodos comparativos. A validação dos métodos foi realizada por adição de padrão e recuperação e por comparação de métodos, no caso da FUR e da BMT, obtendo-se recuperações entre 98,0 e 115,3% para os métodos de quantificação da furosemida e entre 93,0 e 102,0% para o método de quantificação da bumetanida. O método de coleta de GSR é baseado na utilização de membranas finas de celulose bacteriana desenvolvidas pelo Grupo de Materiais Fotônicos do IQ-UNESP.Para os GSR foram realizadas 40 coletas totais em tempos de coleta após o disparo (diferentes e conhecidos), sendo sua comparação realizada através das curvas analíticas, mostrando ser possível a detecção do tempo de disparo com uma margem de erro de aproximadamente 5 minutos. Os resultados foram comparados estatisticamente e os valores obtidos a partir de testes estatísticos mostraram que os métodos podem ser usados para análises de rotina em laboratórios forenses.
This work describes the development of analytical methods for the quantitative determination of furosemide and bumetanide in urine samples using diffuse reflectance spectroscopy (for furosemide) and scanning imaging with quantification by color histogram using RGB color pattern (for both). It involves also the development of a quantitative method for the detection of lead in gunshot residues (GSR) in the hands of the shooters using bacterial cellulose membranes as substrate collection, aiming the discovery of shooting time. It is also done the quantification of lead in progressive hair lotions samples using a previously developed method, aiming the detection of products adulterations and quality control. It also studies the potentiality of the usage of bacterial cellulose membranes for the collection of fingerprints. The developed methods are consisted in the reaction of furosemide (FUR) with the cromogenic reagent p-dimethylamino cinnamaldehyde (p-DAC) 0.70% and hydrochloric acid (HCl) 1.72 mol L-1 in qualitative filter papers with hydrophobic barrier, with spectrophotometric detection and by color histogram; in the reaction of lead(II) ion (Pb2+) with sodium rhodizonate (ROD) 0.16% in micellar medium of sodium dodecyl sulfate (SDS) 5 mmol L-1 in bacterial cellulose membranes with spectrophotometric detection and by scanning electron microscopy; in the reaction of bumetanide (BMT) with the reagent p-dimethylamino cinnamaldehyde (p-DAC) 0.6% and hydrochloric acid (HCl) 0.27 mol L-1 in qualitative filter papers with hydrophobic barrier with color histogram detection an in the collect of fingerprints using bacterial cellulose membranes impregnated with ninhydrine, silver nitrate or zinc oxide, of which the silver nitrate and ninhydrin acted as reasonable collection agents. All concentrations were optimized through chemometrics designs. The reactions were carried out as spot test, involving the formation of a colored product at 545 nm for lead, in 585 nm for furosemide and in 520 nm for bumetanide. Analytical curves were built from standard solutions of the respective analytes. The methods developed for furosemide and bumetanide were applied in fortified synthetic and natural urine samples and the results obtained were compared statistically with comparative methods. The validation of the methods were performed by standard addition and recovery and by comparison of methods, for FUR and BMT, yielding recoveries between 98.0 and 115.3% for furosemide quantification methods and between 93.0 and 102.0% for the quantification method for bumetanide. GSR collection method is based on the use of thin membranes of bacterial cellulose developed by Photonic Materials Group IQ-UNESP. For GSR, 40 total collections were carried out in known and different times of collection after shooting times and their comparison through analytical curves were done, showing the possibility of the detection of the shooting time with an error of 5 minutes, approximately. The results were statistically compared and the values obtained from statistical tests showed that the methods can be used for routine analysis in forensic laboratories.

Drug absorption, elimination and effect may be influenced by many factors including type of formulation, particle size, dissolution and by the presence of other drugs or food and fluid ingestion. The influence of some of these factors on the absorption and effect of frusemide and bumetanide have been investigated in the present studies. The effect of food on the absorption of oral frusemide (40 mg) was determined in 8 healthy volunteers. Food significantly reduced peak plasma concentrations (2.35±0.49 versus 0.51±0.19 mg/l) and delayed the time to peak. The bioavailability of frusemide was also significantly reduced from 76% fasting to 42% after food. The study was then repeated in 9 healthy volunteers using oral bumetanide (2 mg) given with and without food. The peak concentration was reduced after food (96.9±15.1 versus 36.1±11.5 μg/l) and the time to peak concentration delayed. However the mean bioavailability of bumetanide was not significantly reduced by food. A survey carried out in two medical wards within the Edinburgh Royal Infirmary then provided information on the general use of frusemide and bumetanide and showed that most of the patients were taking a single oral dose of diuretic with or in close proximity to breakfast, a situation which could potentially alter diuretic absorption and effect. Consequently, the effect of hospital breakfast on the absorption and efficacy of frusemide was studied in 10 medical inpatients. However when frusemide was administered 2 hours after breakfast, no significant improvement in area under the plasma concentration time curve, urinary recovery of frusemide or total natriuretic and diuretic response was found.

The pharmacokinetics of three unrelated compounds, bumetanide (a diuretic), lorazepam (an anxiolytic) and clofibric acid (an antihyperlipidaemic agent), were investigated in two species of non-human primates commonly used in risk assessment studies. Each of the three drug substances used was independently administered at each of three dose levels, the lowest selected to correspond with the human therapeutic dose (normalised for body weight) and the highest, at ten times the therapeutic dose, selected to approximate to a dose level which might be used during chronic toxicity tests. By use of three dose levels, it was possible to assess whether any non-linear changes in pharmacokinetics occurred between "pseudo-therapeutic" dose levels and those likely to be used during risk assessment studies. Two routes of administration, intravenous and oral, were used at each dose level, the former to establish the basic pharmacokinetics of each compound, the latter to assess the absorption characteristics of the drugs and the systemic availability after oral dosing. Sensitive and specific highperformance liquid chromatographic assays were developed for the quantitative measurement of the compounds of interest. In both the cynomolgus monkey and the baboon, the pharmacokinetics -1 of bumetanide was linear over the dose range examined (O.03-0.3Omg.kg ) after either intravenous or oral administration. The pharmacokinetics -1 of lorazepam (dose range O.05-0.50mg.kg ) was also linesr after intravenous dosing, but the extent of bioavailability after oral administration was non-linear. The pharmacokinetics of clofibric acid (dose range 15-150mg.kg-l ) was non-linear (dose-dependent) by either route of administration. The pharmacokinetics of the three drug substances in the two non-human primate species investigsted were compared with published pharmacokinetic data for these compounds in other animal species, including man. The use of the non-human primate as a "predictive model" for the pharmacokinetics of these compounds in humans is considered in relation to these comparative data and the role of "toxicokinetics" in the design and interpretation of toxicity studies during safety evaluation of drugs is discussed.