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1
McCarron, Philip. "Chiral separations using chiral amino acid ionic liquids." Thesis, Queen's University Belfast, 2016. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.707833.
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The backbone of this work is to make a chiral ionic liquid with enantioselective properties. It is envisaged that the ionic liquid will be a component part of a gel matrix, or membrane, which holds a racemic drug in solution, and shows preferential affinity to one enantiomer. This would allow favoured diffusion of the unattached enantiomer, and such a system would be ideal as the reservoir in a drug delivery system. To test this idea, chiral amino acid ionic liquids were used. The thesis introduces ionic liquids by definition, classification, properties and industrial applications, and also the anti-inflammatory drug ibuprofen as the model test compound. The main application, discussed in Chapter 2, was the separation of ibuprofen enantiomers using chiral amino acid ionic liquids as the chiral selector with liquid-liquid extractions. Ionic liquid preparation is included in Chapter 3, as is an overview of HPLC analysis. Chiral interactions may depend on many factors, and these are explained in Chapter 4. Interaction experiments were performed, and techniques complementary to HPLC also explored. Chapter 5 highlights the subtle nature of enantiomeric separations. Here, an increase in enantiomeric excess percentage by physical processes was demonstrated using ionic liquid test strips. They were developed to help determine enantiomeric excess of ibuprofen as it passed through a series of ionic liquid impregnated sections on paper or silica. In Chapter 6, the analytical and preparative technique of countercurrent chromatography is discussed. It concludes with an application that used a thiouronium based ionic liquid to resolve racemic mandelic acid. Overall, the aim was not to develop and optimise a specific application, but to demonstrate proof-of-principle for using chiral ionic liquids to achieve enantiomeric separation. Two new methodologies were unambiguously demonstrated: the use of paper strips and countercurrent chromatography, and both appear to be worthy of future development.
2
Borgsmiller, Karen McNeal. "Synthetic membranes for chiral separations." Diss., Georgia Institute of Technology, 1999. http://hdl.handle.net/1853/11824.
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3
Olsson, Jeanette. "New Techniques for Chiral Separations." Doctoral thesis, Karlstad : Faculty of Technology and Science, Chemistry, Karlstads universitet, 2008. http://www.diva-portal.org/kau/abstract.xsql?dbid=1594.
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Haglöf, Jakob. "Enantiomeric Separations using Chiral Counter-Ions." Doctoral thesis, Uppsala universitet, Avdelningen för analytisk farmaceutisk kemi, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-130049.
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This thesis describes the use of chiral counter-ions for the enantiomeric separation of amines in non-aqueous capillary electrophoresis. The investigations have been concentrated on studies of the influence, of the chiral counter-ion, the solvent, the electrolyte and the analyte, on the enantioselective separation. Modified divalent dipeptides have been introduced in capillary electrophoresis for the separation of amino alcohols and chiral resolution of amines. Association constants for the ion-pair between dipeptide and amino alcohol could be utilized for development of separation systems with higher amino alcohol selectivity. Chiral discrimination (ion-pair formation) between the dipeptides and amines are preferably generated in non-aqueous background electrolytes (BGEs). The amount of triethylamine in the BGE determined the dipeptide charge and a divalent dipeptide promoted higher enantioselectivity than a monovalent dipeptide. An N-terminal-end blocking group and glutamic acid at the C-terminal-end of the dipeptide was important for chiral separation of the amines. Chemometric and univariate methods have been employed for evaluation of suitable solvent compositions in the BGE. An experimental design including a single solvent as well as binary, ternary and quaternary mixtures of polar organic solvents, showed that optimal enantioresolution was obtained with an ethanol:methanol 80:20 mixture in the BGE. Furthermore, water was found to have an adverse influence on enantioselectivity and no enantioresolution was obtained with BGEs containing more than 30 % water. An alkali metal hydroxide added to the BGE affected the chiral separation by competing ion-pair formation with the selector. The electroosmosis was reduced in order of decreasing alkali metal ion solvated radius and became anodic using K, Rb or Cs in ethanolic BGEs. The correlation between the amino alcohol structure and the enantioselectivity was investigated using chemometrics. The obtained models showed that enantioselectivity for the amino alcohols was promoted by e.g. degree of substitution and substituent size on the nitrogen.
5
Sun, Qian. "Studies of Enhanced-Fluidity Liquids for Chiral Separations." The Ohio State University, 2000. http://rave.ohiolink.edu/etdc/view?acc_num=osu1420637683.
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6
Pickering, Paul. "Selective extraction of (D)-phenylalanine from aqueous racemic (D/L)-phenylalanine by chiral emulsion liquid membrane extraction." Thesis, University of Bath, 1994. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.481450.
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7
Cabusas, Maria Elena Ybarbia III. "Chiral Separations on HPLC Derivatized Polysaccharide CSPs: Temperature, Mobile Phase and Chiral Recognition Mechanism Studies." Diss., Virginia Tech, 1998. http://hdl.handle.net/10919/30426.
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Direct chiral separations of the non-steroidal drugs of 2-methylarylpropionic acids (profens) on the chiral stationary phases (CSPs) of amylose tris(3,5-dimethylphenyl-carbamate), Chiralpak AD, and cellulose tris(3,5-dimethylphenylcarbamate), Chiralcel OD, were investigated. Chiralpak AD and Chiralcel OD are CSPs coated on silica gel and have the same type of constituents. However, they have different higher order structures arising from their different arrangements of the glucose units, i.e., the former has an a-(1,4)-D-glucose linkage and the latter has a b-(1,4)-D-glucose linkage. The orders of optimum enantioselectivity of racemic acids were reversed on the two CSPs which demonstrated that the enantioseparating abilities of these CSPs are complementary. This phenomenon also confirmed that the chiral recognition abilities of both CSPs were dependent on their higher order structures.
Mechanisms for retention and chiral recognition for the separation of racemic 2-methylarylpropionic acids on Chiralpak AD and Chiralcel OD were explored. In depth studies of the dependence of retention and enantioselectivity on temperature and mobile phase compositions were made. The thermodynamic parameters, the differences in free energy, enthalpy, and entropy of association between enantiomers and the CSP were evaluated.
The results indicated that the retention of racemic acids on both CSPs is mainly dependent on the hydrogen bonding interaction between the acid proton of the carboxyl moiety of the analyte and the carbonyl oxygen of the carbamate moiety of the CSP. The chiral recognition mechanism for Chiralpak AD involves: (1) the formation of transient diastereomeric analyte-CSP complexes through hydrogen bonding interactions between the carboxyl and the carbamate moieties of the acid and CSP, respectively; (2) stabilization of these complexes by insertion of the aromatic portion of the analytes into the chiral cavities of the CSP, as well as pi-pi, dipole-dipole, and additional hydrogen bonding interactions between analyte and CSP; and (3) chiral discrimination between enantiomer analytes arising from the additional hydrogen bond between analyte and CSP.
For Chiralcel OD, the chiral recognition mechanisms involve: (1) the formation of transient diastereomeric analyte-CSP complexes through hydrogen bonding interactions between the carboxyl and the carbamate moieties of the acid and CSP, respectively; (2) stabilization of these complexes by insertion of the aromatic portion of the analytes into the chiral cavities of the CSP, as well as pi-pi and dipole-dipole interactions between analyte and CSP; and (3) chiral discrimination due to: (a) the difference in the steric fit of enantiomers into the chiral cavity of the CSP (entropy controlled); and (b) dipole-dipole or p-p interactions between enantiomer analytes and CSP (enthalpy controlled).
Chromatographic and quantitative thermodynamic data showed that there are at least two different chiral recognition mechanisms for Chiralcel OD. One mechanism was characterized by negative values for the enthalpy and entropy differences of the association between enantiomers and CSP that classifies the enantioseparation to be enthalpy controlled. This behavior was exhibited by racemic 2-methylarylpropionic acids with fused rings that were favorably separated at low temperatures. The other mechanism was associated with positive values for the enthalpy and entropy differences of the association between enantiomers and CSP, and the enantioseparation is said to be entropy controlled. The analytes with "free" phenyl moieties favored high temperatures for their enantioseparations.
Both studies on the effects of temperature and mobile phase composition also indicated that the higher order structures of CSPs influence their chiral recognition abilities.Ph. D.
8
Zhong, Qiqing. "Chemical separations by distillation and chiral high performance liquid chromatography." [Ames, Iowa : Iowa State University], 2006.
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9
Olceroglu, Ayse Hande. "Chiral Separations By Enzyme Enhanced Ultrafiltration: Fractionation Of Racemic Benzoin." Master's thesis, METU, 2006. http://etd.lib.metu.edu.tr/upload/12607460/index.pdf.
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In this study, a methodology for separation of chiral molecules, by using enhanced ultrafiltration system was developed. Benzoin was the model chiral molecule studied.
In the scope of developing this methodology, some parameters were investigated in the preliminary ultrafiltration experiments in order to set the operation conditions for enhanced ultrafiltration experiments. Due to the slight solubility of benzoin in pure water, 15% (v/v) Polyethylene glycol (PEG 400) and 30 % (v/v) Dimethyl sulfoxide (DMSO) were selected as cosolvents. Because of the high retention capacity of RC-10000 Da membranes for benzoin, a membrane saturation strategy was developed.
In polymer enhanced ultrafiltration (PEUF) experiments bovine serum albumin (BSA) was used as ligand. Effects of ligand concentration and pH on total benzoin retention and on enantiomeric excess (ee %) were investigated. Benzoin concentration was almost kept constant at ~10 ppm and ~50 ppm for 15% (v/v) PEG 400 and 30 % (v/v) DMSO cosolvents, respectively. It was observed that the increase either in pH or in BSA concentration yielded an increase in total benzoin retention. In 15% (v/v) PEG 400-water, with BSA concentration of 10000 ppm, at pH 10, total benzoin retention reached to 48.7%. For this cosolvent, at different pH values and at different BSA concentrations, all ee % values were about or less than 10%. When 50000 ppm BSA was dissolved in 30 % (v/v) DMSO-water, total benzoin retention increased to 41.3% at pH 10 and ee % reached 16.7 % at pH 11.
In enzyme enhanced ultrafiltration (EEUF) experiments, specific to benzoin, apo form of Benzaldehyde Lyase (BAL, E.C. 4.1.2.38) was used as ligand. These experiments were performed with constant ~ 10 ppm benzoin concentration in only 15% (v/v) PEG 400 &ndashwater solvent. Effect of BAL concentration on total benzoin retention and ee% was investigated. It was found that
for all the studied BAL concentrations in the range of 650- 1936 ppm total benzoin retention and ee % were kept almost constant at ~75% and ~60%, respectively.
10
Carter-Finch, Annabelle Suzanne. "The investigation of achiral and chiral separations by capillary electrochromatography." Thesis, Imperial College London, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.327053.
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11
Wickramanayake, Priyanga, and s3028858@student rmit edu au. "Applications of chiral selectors and replaceable supports for capillary electrophoretic separations." RMIT University. Applied Chemistry, 2007. http://adt.lib.rmit.edu.au/adt/public/adt-VIT20080617.115607.
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The popularity of capillary electrophoresis (CE) as a separation technique has been established over the years. CE offers the advantages of high resolution, high separation efficiency, fast approaches of method development, a range of operational modes and low consumption of reagents. The strategy employed here for the development of chromatographic separations involved the utilization of experimental designs, multi-linear regression and response surface methodology to build empirical models that related the chromatographic quality to the factors influencing the separation. Separation of Nitrofuran antibiotics (NFAs) and their metabolites (NFMs) by using micellar electrokinetic capillary chromatography was successfully completed. The best conditions found to give optimum resolution from the optimization study was pH 9.0, 80 mM SDC concentration, 16 kV with running buffer consisting of 20 mM borate and 20 mM phosphate concentration using a 73 cm x 75 Ým column, resulting in completely resolved NFAs and NFMs within 16 min. It is interesting that all the compounds can be reliably separated with the one mixture, and single CE condition. Whilst all antibiotics have shorter migration time than their respective derivatised metabolites, as a group apart from nitrofurantoin the antibiotics elute before the metabolites. The analytical figures of merit for CE analysis exhibited excellent reproducibility of absolute and relative migration times, and acceptable reproducibility of relative response areas. Successful separation of metabolite derivatives was achieved when the developed method was applied to a spiked prawn sample. The chiral separation of Triadimenol was successfully completed using micellar electrokinetic capillary chromatography. The best conditions found to give optimum resolution from the optimisation study were pH 6.0, 20% methanol, 50 mM SDS concentration, 18 kV with running buffer consisting of 20 mM borate and 20 mM phosphate concentration using a 64.5 cm x 50 Ým column, resulted in baseline resolution of all Triadimenol isomers within 18 min. The optimised separation conditions were applied to a blank grape sample and to a spiked grape sample. No peaks were observed in the blank grape sample whereas the spiked grape sample had two diastereoismer peaks with poor detection sensitivity. Increase in detection sensitivity is necessary to determine the possibility of resolution of all the isomers of Triadimenol, in the spiked grape sample and the blank. Online preconcentration techniques were attempted to for Triadimenol isomer separation. When using online preconcentration technique of sweeping, a 30-fold increase in detection sensitivity of Triadimenol was observed compared to MEKC mode. However enantiomer separation was not possible with sulfated-£]-CD chiral selector. The best conditions were found to be pH 2.5, 50 mM SDS concentration, -20 kV with running buffer consisting of 20 mM phosphate concentration, using a 64.5 cm x 50 Ým column, resulting in diastereoisomer separation within 8 min. Final stage of the project was to create stationary phase beds in capillaries and micro-channels that could be removed and re-created, thus providing a fresh stationary phase. The replaceable stationary phase (RSP) can be used as an operating mode of CE/CEC. Preparation of reversible stationary phase (RSP) inside the capillary column was successfully performed using low methoxy pectin (LMP). LMP renders a capability of reversible thermogelation. Electroosmotic flow (EOF) and sufficient hydrophobicity of LMP gel allow separation of analyates. The porosity of LMP RSP was adequate to support EOF. Successful separation with good reproducibility of areas and migration times was obtained for Caffeine, Aspartame, Benzoic acid, Saccharine (CABS) mixture and NFAs. After performing continuous analyses, the aging of RSP was observed. Temperature was the ¡¥switch¡¦, which applied to remove aged RSP. RSP was recreated for further analysis of analytes. RSP was UV transparent, capable of handling various analytes and diff erent buffer electrolytes including aqueous-organic solvents.
12
Li, Xiaoping. "Thermodynamic and kinetic characterization of chiral separations with ß-cyclodextrin stationary phase." Diss., Connect to online resource - MSU authorized users, 2006.
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13
Booth, Tristan D. "Prediction and description of enantioselective separations on amylose based HPLC chiral stationary phases." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape16/PQDD_0011/NQ36959.pdf.
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14
Witte, Dirk Theodoor. "High performance liquid chromatography for direct and indirect enantiomeric separations of chiral drugs." [S.l. : [Groningen : s.n.] ; University Library Groningen] [Host], 1992. http://irs.ub.rug.nl/ppn/297969609.
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15
Vickers, Paula Jane. "The investigation of chiral separations using normal phase and polar organic capillary electrochromatography." Thesis, Imperial College London, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.405139.
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16
Ferguson, Paul David. "A unified treatment of chiral separations in capillary electrophoresis and liquid phase chromatography." Thesis, University of York, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.387566.
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17
Li, Na. "Resorcinarene-Based Cavitands: From Structural Design and Synthesis to Separations Applications." BYU ScholarsArchive, 2013. https://scholarsarchive.byu.edu/etd/3520.
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Resorcinarenes are cyclic tetramers that are synthesized by the condensation of resorcinol and various aldehydes. The upper and lower rims can be modified with substituents that provide specific selectivity and other chemical features. In this work, resorcinarene-based macrocyclic ligands with specific selectivities have been designed, synthesized and applied to chiral amine discrimination and transition metal ion separations.These resorcinarenes fall into two categories. In the first type, the upper rims of resorcinarenes were modified with amino acid groups, including chiral alanine groups. The lower rims were modified with --CH3, or --C11H23 groups. The structures were studied by nuclear magnetic resonance (NMR), mass spectrometry (MS), dynamic light scattering (DLS), and sustained off-resonance irradiation collision induced dissociation (SORI-CID) techniques in Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS). The binding strength between the resorcinarenes with amines was studied by 1H NMR titration. Among these new resorcinarenes, the chiral alanine undecyl resorcinarenes acid (AUA) showed chiral discrimination among chiral secondary amines. The AUA ligands were adsorbed onto 55% cross-linked styrene-divinylbenzene resin and used as cation-exchangers in ion chromatography (IC) for transition metal ion separations. The AUA IC column showed selectivity for Cu2+ when no chelating eluent was used in the eluent, a selectivity which was not observed with a commercial column containing standard cation-exchangers. Six metal ions (Cu2+, Mn2+, Co2+, Ni2+, Cd2+, and Zn2+) were separated on the AUA column within a reasonable time with a simple oxalic acid gradient eluent. The second type of resorcinarene-based ligand, cyclenbowl, contains four cyclen units on the upper rim and four --C11H23 chains on the lower rim. The column packed with cyclenbowl adsorbed onto polystyrene showed selectivity for Cu2+ over five other transition metal ions including Mn2+, Co2+, Ni2+, Cd2+, and Zn2+ ions. The preconcentration of Cu2+ at the parts per billion level from a high concentration matrix of Mn2+, Co2+, Ni2+, Cd2+, and Zn2+ ions was achieved using HNO3 eluent. Recovery of Cu2+ was greater than 98%. Furthermore, the other five transition metal ions were well separated on the cyclenbowl column with an oxalic acid eluent gradient.
18
Yanes, Santos Enrique Geovani. "STUDIES IN BIOANALYTICAL SEPARATIONS USING CAPILLARY ELECTROPHORESIS AND HIGH PERFORMANCE LIQUID CHROMATOGRAPHY." University of Cincinnati / OhioLINK, 2001. http://rave.ohiolink.edu/etdc/view?acc_num=ucin997383487.
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Nita, Sorin. "Insights into the solvation and selectivity of chiral stationary phases using molecular dynamics simulations and chemical force microscopy." Thesis, Kingston, Ont. : [s.n.], 2008. http://hdl.handle.net/1974/1348.
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Busby, Michael Brent. "Two new, single-isomer, sulfated β-cyclodextrins for use as chiral resolving agents for enantiomer separations in capillary electrophoresis." Texas A&M University, 2005. http://hdl.handle.net/1969.1/3737.
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Two novel, single-isomer, sulfated cyclodextrins, the sodium salts of heptakis(2-
O-methyl-3-O-acetyl-6-O-sulfo)cyclomaltoheptaose (HMAS) and heptakis(2-O-methyl-
6-O-sulfo)cyclomaltoheptaose (HMS) were used as chiral resolving agents in both
aqueous and non-aqueous electrophoretic separation of a set of pharmaceutically active
weak base enantiomers. Enantiomers of twenty one of the twenty four weak bases were
baseline resolved in one or more of the background electrolytes (BGE’s) used.
An eight-step synthetic method was used to produce, on a large scale, the title
compounds in greater than 97% purity. The purity of the synthetic intermediates and the
final products were characterized by HPLC-ELSD and indirect UV-detection capillary
electrophoresis (CE), respectively. X-ray crystallography, MALDI-TOF mass
spectrometry and 1H as well as 13C NMR spectroscopy allowed for unambiguous
characterization of the structure of each intermediate and the final product.
21
Zheng, Jie. "Development of Chiral/Achiral Analysis Methods using Capillary Electrochromatography and Capillary Electrochromatography Coupled to Mass Spectrometry." Digital Archive @ GSU, 2006. http://digitalarchive.gsu.edu/chemistry_diss/6.
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The research presented in this dissertation involves the development of chiral and achiral analysis using capillary electrochromatography (CEC) and CEC coupled to mass spectrometry (CEC-MS). Chapter 1 briefly reviews CEC fundamentals and latest development on chiral CEC and CEC-MS. The CEC-UV enantioseparations for several acidic compounds are described in Chapter 2. The optimum resolutions for these acidic enantiomers are achieved in ion-suppression mode, i.e. with an acidic mobile phase. One of major drawback in coupling CEC with MS is the bubble formation at the column outlet end, resulting in irreproducible retention time and erratic baseline, or even current breakdown. By introducing internal tapered columns, the aforementioned limitations of CEC-MS are successfully overcome in Chapter 3. The CEC-MS enantioseparation of warfarin and coumachlor is carefully investigated and applied to quantify R- and S-warfarin in human plasma. For individual enantiomers, a concentration of 25 ng/mL is detectable. To further improve the robustness of CEC-MS column, a new procedure of fabricating internal tapered columns is reported in Chapter 4. These internal tapered columns demonstrate excellent ruggedness, low background noise, and good compatibility in reversed-phase and polar organic modes of CEC-MS. In chapter 5, the feasibility of using internal tapered columns packed with vancomycin chiral stationary phase (CSP) is explored for simultaneous enantioseparation of eight â-blockers using CEC-MS. After a careful optimization of the mobile phase composition, sheath liquid and spray chamber parameter, 15 out of 16 enantiomers could be simultaneously resolved with excellent efficiency and detection sensitivity. The synthesis and characterization of sulfated and sulfonated cellulose phenylcarbamate CSPs is described in Chapter 6. The use of these CSPs, especially the sulfonated one, significantly enhances the EOF profile and sample throughput but maintain high enantiomeric resolving power under various modes of CEC and CEC-MS. By combining CEC and atmospheric pressure photo-ionization (APPI) MS, Chapter 7 demonstrates the separation and detection of mono-methylated benzo[a]pyrene (MBAP) isomers with ~100 times enhancement on detection sensitivity than CEC-UV. In Appedix 2, monolithic columns are synthesized through photopolymerized sol-gel approach and utilized for CEC and CEC-APPI-MS of polyaromatic hydrocarbons, and alkyl phenyl ketones.
22
Han, Xinxin. "Enantiomeric separations on cyclodextrin-based and synthetic polymeric chiral stationary phases by high performance liquid chromatography and supercritical fluid chromatography." [Ames, Iowa : Iowa State University], 2007.
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23
CATANI, Martina. "Mass transfer characteristics and thermodynamic properties of new generation porous particles for ultrafast, high-efficient separations in chiral and achiral liquid chromatography." Doctoral thesis, Università degli studi di Ferrara, 2018. http://hdl.handle.net/11392/2488045.
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During the last years, there has been a continuous evolution in high performance liquid chromatography (HPLC) aimed at developing high efficient, selective and fast separation methods. One of the main factors affecting the efficiency of a separation is the type of adsorbent used to pack the column since both physico-chemical and geometrical characteristics of packing particles play a key role on column performance. The investigation of
kinetic and thermodynamic properties of porous materials used as stationary phases in LC is of fundamental importance for future developments in
column design and new applications.
It is well known that the efficiency of separation is strongly influenced by
kinetic factors while thermodynamics (adsorption equilibria) affects retention and selectivity. Anyhow, these aspects are very often strictly interconnected to each other.
Adsorption equilibria can be investigated through several chromatographic techniques (e.g. frontal analysis, perturbation method). However, new approaches (”Inverse Method”) allow to estimate the adsorption isotherm of any analyte on a stationary phase by means of only few experimental overloading measurements.
Kinetic factors have been estimated for a long time through the nonlinear fitting of the experimental van Deemter curve. Recently, this approach has been demonstrated to lead to parameters whose physical meaning is debatable. Accordingly, it has been substituted by a more advanced approach which allows to independently estimate each mass transfer contribution. Experimentally, the effective diffusion coefficient of the analyte in the porous medium is calculated by means of stop-flow techniques (peak parking), where analyte molecules are left free to diffuse in the middle of the column when the flow is switched off. The results of peak parking experiments must be then interpreted in the light of a proper model ofdiffusion in porous media.
Mass transfer processes in liquid chromatography can be predicted through
CFD simulations. These studies accurately mimic the band broadening in
specific sections of packed beds. Combined to sophisticated reconstruction of stationary phase structures and the calculation of transport properties in the reconstructed materials, these approaches have permitted to revise some concepts traditionally accepted in the field of diffusion through porous media (such as, for instance, the independence of mass fluxes outside and inside porous particles).
In this thesis, kinetic performance and thermodynamic properties of different types of stationary phases have been explored. Mass transfer kinetics has been firstly investigated in recently introduced sub-2μm monodisperse C18 FPPs for reversed-phase separations characterized by a narrow particle size distribution (nPSD). Then, kinetic performance of new chiral stationary phases (CSPs) for ultrafast separations have been studied by comparing columns in-house packed with both SPPs and sub-2μm FPPs functionalized with the same chiral selector. The results reported in this thesis concern two different studies carried out with two different types of chiral selectors (Whelk-O1 and teicoplanin). Sub-second enantioseparations have been obtained with very short columns packed with these CSPs operated at high flow rates, being an extraordinary result in the field of enantioseparations, unimaginable only few years ago.
On the other hand, the adsorption properties of benzene derivatives on a
perfluorinated adsorbent have been studied by means of nonlinear chromatography measurements in order to investigate the well-known capacity of perfluorinated stationary phases to selectively recognize perfluorinated molecules (”fluorophilicity”), which is usually referred to be active when the molecule contains at least six sp3 perfluorinated carbon atoms.
The results of this study, however, showed that even a single CF3 group
induce a drastic change in the adsorption properties of molecules.Durante gli ultimi anni, il campo della cromatografia liquida ad alta prestazione (HPLC) è stato caratterizzato da una continua evoluzione alla ricerca di nuovi metodi di separazione efficienti, selettivi e veloci. L’efficienza di una separazione è influenzata dalle proprietà chimico-fisiche e geometriche delle particelle che compongono il letto impaccato della colonna. Pertanto, lo studio delle proprietà cinetiche e termodinamiche di questi materiali porosi è fondamentale per lo sviluppo di nuove fasi stazionarie e nuove applicazioni. È noto che l’efficienza di una separazione è influenzata da fattori cinetici, mentre la termodinamica (equilibri di adsorbimento) giocano un ruolo fondamentale per la ritenzione e la selettività, anche se molto spesso questi due aspetti sono strettamente collegati fra di loro. Diverse tecniche cromatografiche (analisi frontale o metodo delle perturbazioni) consentono di indagare gli equilibri di adsorbimento. Recentemente, però, è stato introdotto un nuovo approccio (”Metodo Inverso”) che consente di stimare l’isoterma di adsorbimento di un analita su qualunque fase stazionaria mediante poche misure sperimentali, basate sull’acquisizione di alcuni profili in overloading. I fattori cinetici, invece, sono stati a lungo stimati attraverso il fitting nonlineare della curva sperimentale di van Deemter. Tuttavia, questo metodo porta alla stima di parametri molto spesso privi di senso fisico, pertanto oggi si preferiscono approcci più moderni che consentono la stima indipendente di tutti i contributi al trasferimento di massa. Dal punto di vista sperimentale, i coefficienti di diffusione nella fase mobile e nel mezzo effettivo vengono stimati attraverso la tecnica del ”peak parking”, in cui le molecole di analita vengono lasciate libere di diffondere approssimativamente al centro della colonna in assenza di flusso e i risultati vengono, poi, interpretati mediante un modello di diffusione nei mezzi porosi. I processi di trasferimento di massa in cromatografia possono essere, inoltre, predetti attraverso simulazioni CFD, che mimano accuratamente l’allargamento di banda in una sezione del letto impaccato. Grazie alla combinazione dei risultati derivanti da queste tecniche con quelli di ricostruzione della fase stazionaria, recentemente sono stati rivisitati alcuni concetti come, ad esempio, l’indipendenza dei flussi dentro e fuori dalle particelle. Questa tesi è volta allo studio delle performance cinetiche e termodinamiche di diversi tipi di fasi stazionarie. Inizialmente, la cinetica di trasferimento di massa è stata studiata all’interno di colonne per cromatografia a fase inversa composte da particelle C18 sub-2μm caratterizzate da una distribuzione delle particelle molto stretta. In seguito, sono state studiate le performance cinetiche di nuove fasi stazionarie chirali per cromatografia ultrafast, confrontando colonne impaccate in-house con particelle core-shell e sub-2μm totalmente porose, funzionalizzate con lo stesso selettore chirale. I risultati riportati in questa tesi riguardano due diversi studi effettuati con due diversi tipi di selettore chirale (Whelk-O1 e teicoplanina). Grazie all’utilizzo di colonne corte impaccate con queste nuove fasi stazionarie chirali e alte velocità di flusso, sono state ottenute separazioni di enantiomeri in meno di un secondo. Dall’altro lato, sono stati studiati gli equilibri di adsorbimento di alcuni derivati del benzene su una fase stazionaria perfluorurata attraverso misure di cromatografia nonlineare, allo scopo di investigare la ben nota capacità di queste fasi di riconoscere selettivamente altre molecole perfluorurate (”fluorofilicità”) che contengano almeno 6 atomi di carbonio sp3 perfluorurati. I risultati di questa indagine hanno dimostrato, però che anche un singolo gruppo CF3 è in grado di indurre un drastico cambio negli equilibri di adsorbimento delle molecole sulla fase stazionaria.
24
Rizvi, Syed Asad Ali. "Design of Novel Molecular Micelles for Capillary Electrophoresis." Digital Archive @ GSU, 2006. http://digitalarchive.gsu.edu/chemistry_diss/5.
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The research presented in this dissertation involves the synthesis, characterization, and application of novel anionic and cationic chiral molecular micelles in capillary electrophoresis (CE) for the separation of diverse chiral compounds. Chapter 1 presents brief overview of the surfactants, micelle polymer, CE and micellar electrokinetic chromatography (MEKC). Chapter 2 describes the simultaneous enantioseparation of eight single chiral center â-blockers using two novel leucine and isoleucine based polymeric surfactants. The simultaneous enantioseparation of multichiral center bearing â-blockers, nadolol and labetalol is described in chapter 3. A synergistic approach, using a combination of polysodium N-undecenoxycarbonyl-L-isoleucinate (poly-L-SUCIL) and sulfated â-CD showed dramatic enantioseparation of four stereoisomers of nadolol. On the other hand for labetalol, enantiomeric separation remains unaffected using the dual chiral selector system. Chapter 4 deals with the enantiomeric separation of the binaphthyl derivatives that was found to be influenced by pH, type and concentration of the background electrolyte as well as concentration of the polymeric surfactant. In chapter 5, characterization of five alkenoxy leucine-based surfactants with variations in chain length (C8-C11), polymerization concentration and degree of polymerization showed significant effects on the chiral resolution and efficiency of hydrophobic â-blockers. The synthesis and characterization of two positively charged amino acid derived chiral ionic liquids (ILs) and their corresponding polymers is presented in chapter 6. Chiral separation of two acidic analyte (difficult to resolve with anionic micelles) can be achieved with both monomers and polymers of ILs. In chapter 7, the synthesis and detailed characterization of three pH independent amino acids derived (L-leucinol, L-isoleucinol and L-valinol) sulfated chiral polymeric surfactants is presented. These chiral sulfated surfactants are thoroughly characterized and the morphological behavior of polymeric sulfated surfactants is revealed using cryogenic high-resolution electron microscopy. The work clearly demonstrates for the first time the superiority of chiral separation in MEKC coupled to mass spectrometry at low pH. Finally, in chapter 8, six amino acid derived chiral surfactants with carboxylate and sulfate head groups were compared for enantioseparation of broad range of structurally diverse racemic compounds at neutral and basic pH conditions.
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Rocco, Anna. "Separation of Enantiomers by Means of NanoO-Liquid Chromatography." Doctoral thesis, Lithuanian Academic Libraries Network (LABT), 2013. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2013~D_20130122_144808-59559.
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Nano-liquid chromatography (nano-LC) was selected as analytical tool to develop different methods for chiral separations. Nano-LC offers several advantages over conventional LC, e.g., low sample requirement, short analysis time, easy coupling with mass spectrometer, and use of small amount of reagents, with a consequent low environmental pollution. In case of chiral separations, where expensive chiral stationary phases or chiral mobile phase additives (CMPA) have to be employed, nano-LC results very useful since it allows to perform analysis with small amount of this costly material.
Initially, a derivatized β-cyclodextrin, heptakis (2,3,6-tri-O-methyl)-β-cyclodextrin, was employed as CMPA for the chiral separation of some non steroidal anti-inflammatory drugs. The role of different achiral stationary phases in the separative process was investigated. The employed capillary columns were packed in the laboratory, following the slurry-packing procedure. Subsequently, the performance of a reversed phase C18 particulate packed column was compared with that one of a C18 monolithic column, in combination with cyclodextrins (heptakis (2,3,6-tri-O-methyl)-β-cyclodextrin or hydroxypropyl--cyclodextrin) as CMPA. Finally, hydroxypropyl--cyclodextrin was selected as chiral selector to prepare chiral monolithic columns by one-step synthesis. For this aim, the cyclodextrin was activated as the allyl derivative. The composition of the polymeric mixture of the continuous beds was varied... [to full text]Skysčių nano-chromatografija buvo pasirinkta kaip įrankis kurti įvairius chiralinių junginių atskyrimo metodus. Skysčių nano-chromatografija turi eilę privalumų, lyginant su tradiciniais skysčių chromatografijos metodais, pvz.: mažą bandinio poreikį, trumpą analizės trukmę, suderinamumą su masės spektrometrija ir nedideles tirpiklių, reagentų sąnaudas, todėl mažą aplinkos taršą. Chiralinių junginių analizei atlikti, kai reikalingos brangios chiralinės nejudrios fazės ar chiraliniai judrios fazes priedai, skysčių nano-chromatografija yra ypač naudinga, nes leidžia atlikti analizę su minimaliomis šių brangių medžiagų sąnaudomis. Pirmiausia, derivatizuotas β-ciklodekstrinas, heptakis (2,3,6-tri-O-metil) - β-ciklodekstrinas, buvo panaudotas kaip chiralinis nejudrios fazes priedas kai kurių nesteroidinių priešuždegiminių vaistų enantiomerams atskirti. Buvo įštirtas įvairių achiralinių nejudrių fazių vaidmuo atskyrimo procese. Šiuo tikslu naudojant suspensinį birių dalelių pakavimo metodą laboratorijoje buvo paruoštos kapiliarinės kolonėlės. Vėliau, buvo lyginama C18 biriais sorbentais pakrautų atvirkštinių fazių ir monolitinių kapiliarinių kolonėlių skiriamoji geba, chralinias judrios fazes priedais naudojant ciklodekstrinus (heptakis (2,3,6-tri-O-metil)-β-ciklodekstriną arba hidroksipropil-β-ciklodekstriną). Galiausiai, vienpakopės polimerizacijos būdu buvo gautos chiralines kapiliarines kolonėles, chiralniu selektoriumi naudojant hidroksipropil-β-ciklodekstriną. Šiuo tikslu... [toliau žr. visą tekstą]
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Wang, Ying. "Chiral ionic liquid in chiral separation and catalysis." Thesis, Queen's University Belfast, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.603555.
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In this thesis, the results of synthesis of chiral ionic liquids (ILs) and an investigation of their application in chiral separation and catalysis are described. The study of the chiral lLs application was performed using liquid-liquid extraction, crystallization and asymmetric catalysis with analysis of substrate content and enantioselectivity by High Performance Liquid Chromatography (HPLC) . A series of chiral lLS with chiral cations or chiral anions were synthesized through alkylation or anion exchange with optical pure starting materials as the •chiral pool", Properties of chiral ILS made in house were studied using various techniques, The structures and configurations of the chiral ILs can be altered easily to meet the required physical properties, such as melting point and viscosity, Chiral! ILs made in house show chiral affinity with a range of racemic compounds, In the liquid-liquid extraction of menthol from chiral lL, good extraction is observed from the chiral lL layer into alkane !layer without visible leaching of the chiral lL into the alkane layer. In the mandelic acid resolution by • Dutch resolution", 22 different ILS were used as additive in the chiral selector, In general, ILS exhibit a equalize effect on both yield and ee of the final product. For the asymmetric catalysis study, both Mukaiyama-aldol reaction and Diels-Alder reaction were investigated with Cu(II)-PhBOX and Zn(II)-PhBOX as catalyst. In the Mukaiyama-aldol reaction, chiral ILS can be applied . as ligand and an increased ee is observed as compared with the reactions in the absence of the Il. In the Diels-Alder reaction, addition of the chiral Il 19 (Il of (1R,2S.5R)- menthol) with Zn(II)-PhBOX led to an increase in the endo ee from 5 % in DCM, 68 % in ether and 57 % in pure (C 2mim][NH 10 91 % under homogeneous reaction condition and 95 % in biphasic system with both high conversion and high endo selectivity. The endo selectivity of biphasic system with the chiral lL 1 g, [C2mim][NTf21 and ether is 99 %, which means nearly all product goes into endo form with 95 % ee.
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Tieriekhov, Kostiantyn. "Applications non-conventionnelles de champs magnétiques à séparation chirale et aux systèmes électrochimiques dynamiques." Electronic Thesis or Diss., Bordeaux, 2023. http://www.theses.fr/2023BORD0502.
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L’énantioséparation de précision est essentielle pour les industries pharmaceutiques et alimentaires. Les techniques conventionnelles de séparation chirale offrent un large éventail de méthodes, qui reposent toutes sur des sélecteurs chiraux - des phases stationnaires ou des molécules qui distinguent les énantiomères par une interaction stéréospécifique. Malgré le grand nombre de sélecteurs naturels et synthétiques actuellement utilisés, la demande croissante d’énantiopurité stimule la recherche de nouvelles méthodes polyvalentes.Le but de cette thèse est d'étudier des méthodes alternatives de séparation chirale impliquant l'application de champs magnétiques dans diverses configurations. Une idée est centrée sur le concept de vraie et fausse chiralité, introduit par L. Barron pour les systèmes dynamiques d'objets individuels et de grandeurs physiques vectorielles. Sa discussion indique explicitement que ni les champs magnétiques ni électriques statiques, ni aucune combinaison de ceux-ci, ne possèdent une véritable chiralité, la caractéristique requise pour induire une discrimination énantiomérique. Cependant, sa théorie suggère l’existence d’un analogue moléculaire de l’effet Faraday bien connu sous forme de l’application colinéaire d’un champ magnétique à un flux moléculaire.Alternativement, une configuration perpendiculaire au flux moléculaire impliquant un substrat ferromagnétique a démontré des interactions de spin énantiospécifiques, également connues sous le nom d'effet CISS. À cet égard, notre objectif principal était d’explorer une telle interaction dans des conditions dynamiques d’électrophorèse capillaire, qui permet une détection simple et rapide, tout en introduisant des substrats de Ni le long du flux de molécules et en appliquant un champ magnétique orthogonal.Enfin, la configuration orthogonale du champ magnétique a été exploitée pour étudier le comportement dynamique d'objets électropolarisés. Il a été démontré que la rotation présenté par différents objets sous l'effet magnétohydrodynamique induit par la force de Lorentz dépendent de la polarité du champ magnétique. Leur comportement dynamique en fonction du temps ressemble à celui de systèmes faussement chirauxHigh-purity enantioseparation is essential for the pharmaceutical and food industries. Conventional chiral separation techniques provide a wide range of methods, all of which rely on chiral selectors - stationary phases or molecules that discriminate enantiomers through stereospecific interaction. Despite the vast number of natural and synthetic selectors currently in use, the increasing demand for enantiopurity is driving research for new and versatile methods.The aim of this thesis is to investigate alternative methods of chiral separation that involve the application of magnetic fields in various configurations. One idea centers around the concept of true and false chirality, which was introduced by L. Barron for dynamic systems of individual objects and physical vector quantities. His discussion explicitly states that neither static magnetic nor electric fields, nor any combination of those, possess true chirality, the feature required to induce enantiomeric discimination. However, his theory suggests a molecular analog of the well-known Faraday effect based on the collinear application of magnetic field to a molecular flow.Alternatively, a perpendicular configuration with the molecular flow involving a ferromagnetic substrate has demonstrated enantiospecific spin interactions, otherwise known as the CISS effect. In this regard, our main objective was the further exploration of such interactions in dynamic conditions of capillary electrophoresis, which provides simple and fast detection, while introducing Ni substrates along the flow of molecules and applying an orthogonal magnetic field.Lastly, the orthogonal configuration of the magnetic field was exploited to study the dynamic behavior of electropolarized objects. The patterns of the resulting rotation, exhibited by different objects under the influence of a magnetohydrodynamic effect, originating from the induced Lorentz force, are shown to be dependent on magnetic field polarity. Their dynamic behavior as a function of time resembles those of falsely chiral systems
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Ye, Yun Kui. "Chiral separation with polysaccharide based amylose tris(3,5-dimethylphenylcarbamate) chiral stationary phase." Access to citation, abstract and download form provided by ProQuest Information and Learning Company; downloadable PDF file, 131 p, 2006. http://proquest.umi.com/pqdweb?did=1037888881&sid=1&Fmt=2&clientId=8331&RQT=309&VName=PQD.
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Huang, Xingye. "Chiral separation of pharmaceuticals by capillary electrophoresis." Thesis, University of Nottingham, 2010. http://eprints.nottingham.ac.uk/11645/.
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Conventional capillary zone electrophoresis (CZE) methods, with simple buffer solute, natural or derivatized cyclodextrin and organic additive in BGE, have been developed for a group of ten standard chiral pharmaceutical compounds representing different physiochemical properties and pharmaceutical activities. In this study, factors affecting chiral separation in CZE, including BGE pH value, ionic strength, chiral selector type, selector concentration and organic additives, were optimized. A maximum of eight standard compounds were separated by three different standard methods which were developed. The electrophoretic behaviours of the standard compounds observed were in good agreement with the literature. Partial filling technique (PFT) was studied as a complementary approach to conventional CZE methods for enantioseparation of standard compounds. Partial filling time, selector type and concentration were investigated; a maximum of seven standard compounds were separated by optimized filling time and three different chiral selectors. However, for five of the separated pharmaceuticals, the chiral resolutions achieved were much lower than those obtained from conventional CZE methods. Key observations from the experiment were supported by previous research. For the first time, glycidol was evaluated as a covalently bonded coating material on CE capillary for enantioseparation. Hyperbranched polyglycidol brushes were grown directly from Si/SiO2 surface via anionic ring-opening polymerization, using surface Si-OH groups as initiator. This grafting-form technique eliminated the need for initiator functionalized self-assembled monolayers on the surface, and the thickness and complexity of the hyperbranched polymer brushes could be well controlled in this process. Polyglycidol coating was established on the surface of glass slides and then adapted to CE capillary. Both fused silica capillary and etched capillary were used to examine the electrophoretic properties of polyglycidol coating. Chiral polyglycidol coating was compared with the standard CZE method developed and showed excellent chiral selectivity for standard compounds. Nine out of ten standard compounds were separated with poly-S-glycidol coated capillary, using simple buffer solute containing organic additive. Application of etched capillary further improved the enantioseparation resolution and peak efficiency for those standard compounds. Stability and coating regeneration ability were studied. Polyglycidol coating developed on CE capillary gradually lost its chiral selectivity after 50 30-min runs with acidic BGE. Coating regeneration on the remaining surface was difficult. The result indicated that glycidol isomer can be used as monomer for in situ polymerization in CE capillaries and the coating formed on the inner surface has potential chiral selectivity toward various pharmaceuticals, which is equal or better than traditional chiral CE.
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Wu, Zecai. "Enantiomeric purity determination using dual polarimetric and absorbance detection." Thesis, University of York, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.306467.
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Layton, Sherry E. "Comparison of various chiral stationary phases for the chromatographic separation of chiral pharmaceuticals /." Electronic version (PDF), 2005. http://dl.uncw.edu/etd/2005/laytons/sherrylayton.pdf.
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Prangle, Anita Susann. "Chiral drug bioanalysis using reduced-dimension separation systems." Thesis, University of Sunderland, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.369863.
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Svang-Ariyaskul, Apichit. "Chiral separation using hybrid of preferential crystallization moderated by a membrane barrier." Diss., Georgia Institute of Technology, 2010. http://hdl.handle.net/1853/33909.
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The major innovation of this work is an establishment of a novel chiral separation process using preferential crystallization coupled with a membrane barrier. This hybrid process was proved to be promising from a significant increase in product yield and purity compared to existing chiral separation processes. This work sets up a process design platform to extend the use of this hybrid process to a separation of other mixtures. This novel process especially is a promising alternative for chiral separation of pharmaceutical compounds which include more than fifty percent of approved drugs world-wide. A better performance chiral separation technique contributes to cut the operating cost and to reduce the price of chiral drugs.
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Ardid, Candel M. "Experimental and theoretical investigation of chiral separation by crystallisation." Thesis, University College London (University of London), 2014. http://discovery.ucl.ac.uk/1429288/.
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Chiral molecules often show different pharmacological and toxicological properties, making their separation crucial for pharmaceutical companies. The resolution of racemic mixtures is often achieved via crystallisation methods. The lack of experimental data has been a major constraint in validating proposed computational methods for aiding the design of crystallisation processes for chiral resolution. This thesis provides both structural and thermodynamic data, and uses it to assess the limitations of current computer modelling methods. Progress in computational methods might eventually result in the design of resolving agents and hence reduce production costs of drugs and fine chemicals. Previous studies of naproxen have concentrated on the marketed enantiopure form of this anti-inflammatory drug. A crystallisation screen was conducted to identify all possible crystal phases of racemic and enantiopure naproxen. No polymorphs were detected and the crystal structure of the racemic compound was solved from powder X-ray diffraction data. The nature of the racemic species was confirmed with thermal methods, and differential scanning calorimetric and solubility measurements were used to estimate the enthalpy difference between the crystals at 156 °C and in the range of 10 to 40 °C. These data were used to test the different approximations involved in determining the energy differences between the racemic and enantiopure crystals. An extensive crystallisation screen was also performed for (1R,2S)-ephedrine 2-phenylpropionate salts. The crystal structure of the least soluble salt and three polymorphs of the most soluble salt were determined by low temperature single crystal X-ray diffraction or powder X-ray diffraction. Solubility measurements and differential scanning calorimetry were used to determine the relative stability of the salt pairs and polymorphs. These results showed the inadequacies of lattice energy calculations of the diastereomeric salt pair and their polymorphs. Experimental work on related diastereomeric salt pairs emphasised the difficulty in fully structurally and thermodynamically characterising these systems.
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Ma, Li. "Influence of experimental parameters on chiral separation in SFC." Thesis, Loughborough University, 1994. https://dspace.lboro.ac.uk/2134/32255.
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This thesis describes an investigation of the chiral separation of two groups of molecules by supercritical fluid chromatography (SFC). The studies were carried out on chiral ChiralCel OB and OD, Cyclobond RN-I and -III and on Pirkle columns using a range of pressure and temperatures from subcritical liquid carbon dioxide to supercritical conditions with or without the addition of methanol (or 2-propanol) as a mobile phase modifier. The first study examined the relationship between structure and resolution for a number of chiral substituted benzyl alcohols and related compounds. The second study examined the benzodiazepines, which have been chromatographed by SFC previously in this laboratory, as examples of fairly polar drugs.
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Padmanaban, Mohan, Philipp Müller, Christian Lieder, Kristina Gedrich, Ronny Grünker, Volodymyr Bon, Irena Senkovska, et al. "Application of a chiral metal–organic framework in enantioselective separation." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-138682.
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A modular approach for the synthesis of highly ordered porous and chiral auxiliary (Evans auxiliary) decorated metal–organic frameworks is developed. Our synthesis strategy, which uses known porous structures as model materials for incorporation of chirality via linker modification, can provide access to a wide range of porous materials suitable for enantioselective separation and catalysis. Chiral analogues of UMCM-1 have been synthesized and investigated for the enantioseparation of chiral compounds in the liquid phase and first promising results are reportedDieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich
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Padmanaban, Mohan, Philipp Müller, Christian Lieder, Kristina Gedrich, Ronny Grünker, Volodymyr Bon, Irena Senkovska, et al. "Application of a chiral metal–organic framework in enantioselective separation." Royal Society of Chemistry, 2011. https://tud.qucosa.de/id/qucosa%3A27771.
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A modular approach for the synthesis of highly ordered porous and chiral auxiliary (Evans auxiliary) decorated metal–organic frameworks is developed. Our synthesis strategy, which uses known porous structures as model materials for incorporation of chirality via linker modification, can provide access to a wide range of porous materials suitable for enantioselective separation and catalysis. Chiral analogues of UMCM-1 have been synthesized and investigated for the enantioseparation of chiral compounds in the liquid phase and first promising results are reported.Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
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Vaidya, B. K. "Chiral separation of drugs and drug intermediates by immobilized biocatalyst." Thesis(Ph.D.), CSIR-National Chemical Laboratory, Pune, 2009. http://dspace.ncl.res.in:8080/xmlui/handle/20.500.12252/2773.
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Zhang, Shi-Yuan. "Homochiral Metal-Organic Materials: Design, Synthetic and Enantioseletive Separation." Scholar Commons, 2014. https://scholarcommons.usf.edu/etd/5163.
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Owing to the growing demand for enantiopurity in biological and chemical processes, tremendous efforts have been devoted to the synthesis of homochiral metal-organic materials (MOMs) because of their potential applications in chiral separation and asymmetric catalysis. In this dissertation, the synthetic strategies for homochiral MOMs are discussed keeping the focus on their applications. Two distinct approaches have been taken to synthesize chiral structures with different topologies and accessible cavities. The chiral MOMs have been utilized in enantioselective separation of racemates.
Chiral variants of the prototypal metal-organic framework MOF-5, δ-CMOF-5 and [lambda]-CMOF-5, have been synthesized by preparing MOF-5 in the presence of L-proline or D-proline, respectively. CMOF-5 crystallizes in chiral space group P213 instead of Fm-3m as exhibited by MOF-5. The phase purity of CMOF-5 was validated by single crystal and powder X-ray diffraction, IR spectroscopy, TGA, N2 adsorption, microanalysis and solid-state CD. CMOF-5 undergoes a reversible single crystal to single crystal phase change to MOF-5 when immersed in a variety of organic solvents although N-methyl-2-pyrolidone, NMP, does not induce loss of chirality. Indeed, MOF-5 undergoes chiral induction when immersed in NMP, affording racemic CMOF-5.
A pair of homochiral network materials (CNMs), [Co2(S-man)2(bpy)3](NO3)2·guests (1S) and [Co2(R-man)2(bpy)3](NO3)2·guests (1R) based upon S-mendelic acid and R-mendelic acid were synthesized and characterized, respectively. The cationic networks contain 1D homochiral channels with the cross section of 8.0 Å × 8.0 Å. The chiral amphiphilic channel surfaces lined with hydrophilic nitrate anions and hydrophobic phenyl groups are capable for multiple interactions with guest species. Chiral resolution of 1-phenyl-1-propanol (PP) enantiomers was performed utilizing the homochiral porosity of 1S and 1R through different time period at different temperatures with/without additives. The mechanism for enantioselective separation of PP was fully investigated through single crystal structural analysis of guest exchanged 1S and 1R. Chiral resolution of PP revealed enhanced performance with additive, which can significantly improve the ee value from 32% to 60%.
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Liang, Yufu. "Chiral Separation Using Capillary Electrophoresis (CE) and Continuous Free Flow Electrophoresis (CFFE)." University of Cincinnati / OhioLINK, 2003. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1067615432.
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He, Jun. "Chiral Analysis Using Capillary Electrophoresis Coupled to Mass Spectrometry: Development of Novel Modes and Applications Using Molecular Micelles and Surfactant-Bound Monolithic Columns." Digital Archive @ GSU, 2011. http://digitalarchive.gsu.edu/chemistry_diss/61.
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Micellar electrokinetic chromatography (MEKC) and capillary electrochromatography (CEC) are two of the major capillary electrophoresis (CE) modes that have been interfaced to mass spectrometry (MS) for sensitive and selective analysis of chiral compounds. This research combines these two modes and expands their applications in chiral CE analysis. Chapter 1 is a review of amino acid based molecular micelles used in MEKC-MS for enantioselective analysis over the past five years. In this chapter, a typical MEKC-MS experiment setup as well as detailed standard operating procedure in synthesis of molecular micelles and running a typical MEKC-MS experiment using the molecular micelles is discussed. Chapter 2 described a multivariate MEKC-MS optimization for the simultaneous analysis of two negatively charged model chiral compounds in negative ion mode with molecular micelles. In this chapter, a central composite design (CCD) is used to first construct a series of experiments to optimize all the important MEKC-MS parameters. Next, response surface methodology (RSM) was used to analyze the interactions between the factors, picking up the best separation and detection conditions, predicting the result of the chiral separation/MS detection, and finally running the actual experiment and comparing the chromatographic results with the predicted parameters. Chapter 3 demonstrates a similar multivariate MEKC-MS optimization for analysis of a positively charged model chiral compound in a positive ion mode. The same CCD and RSM methods were used to optimize the separations and MS sensitivity. Chapter 4 describes a chiral analysis of four neutral benzoin derivatives (hydrobenzoin, benzoin, benzoin methyl ether, and benzoin ethyl ether) using MEKC coupled to atmospheric pressure photo-ionization mass spectrometry (APPI-MS). The same multivariate experimental design strategy was used to optimize the MEKC as well as APPI-MS parameters. Simultaneous chiral separation of all four benzoin derivatives was achieved with high detection sensitivity compared to UV-detection. Chapter 5 introduces a novel one-pot synthesis scheme for an acryloyl-terminated, carbamate-linked surfactant-bound monolith with leucine head group and different chain lengths. The method promises to open up the discovery of new amino acid based polymeric monoliths for chiral separations and enhanced chemoselectivity for simultaneous chiral separations and enhanced detection in CEC and CEC-MS. In Chapter 6, five amide-linked surfactant-bound monoliths with different chain lengths and head groups (leucine, valine, and phenylalanine) were synthesized and characterized. Enantioseparation of several test compounds was achieved by CEC using the monolithic columns. One of the chiral surfactant, sodium 11-acrylamidoundecanoyl-L-leucinate (SAAUL), was polymerized in aqueous solution under 60Co radiation to form molecular micelle poly-SAAUL. MEKC experiments were carried out with the poly-SAAUL molecular micelle to separate ten cationic chiral compounds. The result was compared with the CEC separation using the AAUL monolithic column. This study is the first comparison of chiral CEC and MEKC with the same surfactant monomer, which has the capability of forming both chiral stationary phase for CEC and chiral pseudophase for MEKC.
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Rimmer, Duncan Adam. "Novel asymmetric microenvironments for separation of enantiomers chiral drugs and natural products." Thesis, Open University, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.254965.
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Fernandes, Andreia Patrícia Macedo. "Separation of mandelic acid enantiomers using aqueous biphasic systems containing chiral selectors." Master's thesis, Universidade de Aveiro, 2017. http://hdl.handle.net/10773/22869.
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Mestrado em Bioquímica - Métodos BiomolecularesA quiralidade é a uma propriedade importante na indústria farmacêutica, uma vez que um enantiómero de um fármaco pode exercer o efeito terapêutico desejado enquanto o outro pode ser inerte ou mesmo nefasto. Embora vários fármacos sejam comercializados na sua forma racémica, as entidades regulatórias aconselham o desenvolvimento de fármacos enantiomericamente puros e mais seguros. Neste contexto, a indústria farmacêutica procura formas baratas e eficientes de produzir fármacos enantiomericamente puros, sendo este o objetivo da presente tese. A separação enantiomérica do ácido mandélico (AM), aqui utilizado como um fármaco racémico modelo, será tentada recorrendo a sistemas aquosos bifásicos (SABs) constituídos por seletores quirais de origem natural (proteínas e açúcares). Serão usadas duas abordagens: (i) a introdução de proteínas como seletores quirais em diferentes tipos de SABs; e (ii) o uso de (D)-sacarose simultaneamente como seletor quiral e componente de fase em SABs. Na primeira abordagem, foram utilizados diferentes tipos de SABs (polímero+polímero, polímero+sal, sal+líquido iónico (LI), polímero+LI e polímero+açúcar) e duas proteínas (albumina de soro bovino – BSA – e citocromo C – Cit c). A escolha das proteínas assentou em resultados de molecular docking que indicaram interações distintas entre diferentes proteínas e os enantiómeros do AM. Nestas fases, os sistemas constituídos por PPG400+(D)-Sacarose+BSA (excesso enantiómerico de -5.9± 0.5%) e PPG400+dihidrogeno fosfato de colínio+Cit c (excesso enantiomérico de -9.0 ± 1.2%) revelaram-se os mais eficientes. As proteínas e os constituintes de fase dos SABs afetaram a separação enantiomérica de ácido mandélico. Uma vez que a docagem molecular não considera as interações com os componentes de fase, esta abordagem revelou ser incapaz de prever o desempenho das proteínas como seletores quirais em SABs. Com o objetivo de ultrapassar as limitações de seletividade enantiomérica e melhorar a simplicidade operacional da tecnologia proposta, a (D)-sacarose foi usada simultaneamente como formador de fase e seletor quiral em SABs. Depois de uma otimização cuidada, foi possível obter um excesso enantiomérico máximo de -12.3 ± 0.5% com um SAB constituído por polímero e (D)-sacarose.
Chirality is an important property for the pharmaceutical industry, since one enantiomer of a drug can exert a therapeutic action, while the other may be inert or even nefarious. While several drugs are commercialized as racemates, regulatory bodies strongly encourage the development of safer enantiopure drugs. In this context, pharmaceutical industry seeks for cheap and efficient ways of obtaining enantiopure pharmaceuticals and this is the main objective of this thesis. The enantiomeric separation of mandelic acid (MA), here used as a model racemic drug, using aqueous biphasic systems (ABS) composed of natural chiral selectors (proteins and sugars) will be proposed. Two different approaches were used: (i) the introduction of proteins as chiral selectors in several types of ABS; and (ii) ABS formed by D-Sucrose as both phase former and chiral selector. Within the first approach, different types of systems (polymer+polymer, polymer+salt, polymer+sugar, and ionic liquids (ILs)+salt, ILs+polymer) and of proteins (bovine serum albumin –BSA - and cytochrome C – Cyt C) were used. These two proteins were chosen based on molecular docking results that shown distinctive interactions with the two MA enantiomers among eleven screened proteins. PPG400+(D)-sucrose+BSA system (enantiomeric excess of -5.9 ± 0.5%) and PPG+cholinium dihydrogenphosphate+Cyt C (enantiomeric excess of -9.0 ± 1.2% were the most efficient ABS developed up to this stage. Both the protein and ABS phase formers affected the enantioseparation of MA. Since molecular docking does not encompass the interactions with the ABS phase formers, it was limited at predicting the proteins’ performance as chiral selectors in ABS. In order to surpass the limited enantioselectivity displayed and to improve the operational simplicity of the proposed technology, (D)-sucrose was employed as both chiral selector and phase former in ABS. After a proper optimization, it was possible to achieve a maximum enantiomeric excess of -12.3 ± 0.5% with an ABS composed of polymer and (D)-sucrose.
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SPIESER, ESTELLE. "Les separations chirales en presence de beta-cyclodextrines et de polymeres (doctorat : pharmacochimie)." Strasbourg 1, 1998. http://www.theses.fr/1998STR15057.
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Liang, Hongxi. "An investigation into the use of #beta#-cyclodextrins as additives to effect enantiometric separation by reversed phase HPLC." Thesis, Robert Gordon University, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.260042.
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Hedeland, Ylva. "Chiral Separation of Amines by Non-Aqueous Capillary Electrophoresis using Low Molecular Weight Selectors." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Universitetsbiblioteket [distributör], 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-6759.
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Kholany, Mariam Achraf Mohamed Bahie El Din El. "Enantioselective separation of chiral compounds using aqueous biphasic systems and solid-liquid biphasic system." Master's thesis, Universidade de Aveiro, 2017. http://hdl.handle.net/10773/22708.
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Mestrado em Biotecnologia - Industrial e AmbientalTipicamente, apenas um dos enantiómeros é responsável pelo efeito pretendido de um fármaco, sendo que o outro pode levar a respostas menos potentes ou até mesmo indesejadas. As entidades reguladoras praticam políticas restritas em relação à comercialização de fármacos como misturas racémicas. Assim, a indústria farmacêutica tem enfrentado desafios relacionados com o desenvolvimento de métodos para produção de fármacos oticamente puros. No entanto, e considerando a dificuldade acrescida na produção de enantiómeros puros por síntese direta, a síntese de misturas racémicas seguida da sua purificação surge como uma alternativa mais barata, simples e flexível. Os sistemas aquosos bifásicos (SABs) e os sistemas de duas fases sólida-líquida (SDFSL) são técnicas alternativas mais biocompatíveis que têm sido utilizados como técnicas de separação enantiosseletiva de fármacos e/ou aminoácidos com enantiosseletividades bastante promissoras. Para além disso, apresentam benefícios de custo, rapidez, simplicidade e versatilidade de operação e possibilidade de aumento de escala. Este trabalho foca-se no desenvolvimento de SABs e SDFSL constituídos por seletores quirais que possam atuar simultaneamente como solvente. Numa primeira abordagem o objetivo foi desenvolver novos SABs quirais, mais biocompatíveis, simples e eficientes. Para tal, SABs constituídos por açúcares, aminoácidos e líquidos iónicos quirais foram aplicados na resolução enantiomérica de ácido mandélico racémico. O sistema mais promissor, composto por [C1Qui][C1SO4] + K3PO4, obteve um excesso enantiomérico de -33.4%. Numa segunda abordagem, foi possível criar uma alternativa mais simples e mais eficiente recorrendo a SDFSL. Com estes sistemas, foi obtido o valor mais elevado de excesso enantiomérico deste trabalho, de 49.0%, através da precipitação enantiosseletiva do R-ácido mandélico por interação com [N4444][D-Phe].
Conventionally, only one of the enantiomers is responsible for the intended effect of a drug, whilst the other may lead to a less potent or even undesired response. Regulation entities are very strict regarding the commercialization of racemic drugs. Thus, pharmaceutical industry has been facing challenges related to the creation of methods to produce optically active drugs. However, considering the increased difficulty in the production of pure enantiomers by direct synthesis, the synthesis of racemic mixtures followed by their purification appears as a cheaper, simpler and more flexible alternative. Aqueous biphasic systems (ABS) and solid-liquid biphasic system (SLBS) are more biocompatible alternatives that have been used to separate racemic drugs and amino acids with promising enantioselectivities. Furthermore, these are cost-effective, quick, simple and operationally flexible. This work intended to develop ABS and SLBS using chiral selectors that can simultaneously act as solvents. In a first attempt, chiral ABS of better biocompatibility, simplicity and efficiency were developed. For that purpose, ABS constituted by sugars, amino acids and chiral ionic liquids (CILs) were applied for chiral resolution of racemic mandelic acid (MA). The most promising ABS was a system composed of [C1Qui][C1SO4] + K3PO4 which yielded the maximum enantiomeric excess of -33.4%. In a second approach, it was possible to create a simpler and more efficient technique resorting to SLBS. The enantiomeric excess value of 49.0% was achieved, by the enantioselective precipitation of the R-MA caused by interactions with [N4444][D-Phe].
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Wang, Min. "Novel applications of comprehensive two-dimensional gas chromatography and capillary electrophoresis for the chiral discrimination." HKBU Institutional Repository, 2007. http://repository.hkbu.edu.hk/etd_ra/823.
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Carlsson, Björn. "From achiral to chiral analysis of citalopram." Doctoral thesis, Linköpings universitet, Klinisk farmakologi, 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-5217.
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Within the field of depression the “monoamine hypothesis” has been the leading theory to explain the biological basis of depression. This theory proposes that the biological basis of depression is due to a deficiency in one or more of three key neurotransmitter systems, namely noradrenaline, dopamine and serotonin which are thought to mediate the therapeutic actions of virtually every known antidepressant agent. Citalopram is a selective serotonin-reuptake inhibitor (SSRI) used for the treatment of depression and anxiety disorders. Citalopram is a racemic compound, in other words composed of a 50:50 mixture of two enantiomers (S-(+)-citalopram and R-(-)-citalopram) and with one of the enantiomers (S-(+)-citalopram) accounting for the inhibitory effect. At the time of introduction of citalopram the physician needed a therapeutic drug monitoring service to identify patients with interactions, compliance problems and for handling questions concerning polymorphic enzymes and drug metabolism. An achiral analytical separation method based on solid-phase extraction followed by high-performance liquid chromatography (HPLC) was developed for routine therapeutic drug monitoring (TDM) of citalopram and its two main demethylated metabolites. As the data available on citalopram were from achiral concentration determinations and to be able to further investigate citalopram enantiomers effects and distribution, a chiral method for separation of the enantiomers of citalopram and its demethylated metabolites was established. The advances within chiral separation techniques have made measurement of the concentrations of the individual enantiomers in biological fluids possible. The process behind enantioselective separation is however not fully understood and the mechanism behind the separation can be further scrutinized by the use of multivariate methods. A study of the optimization and characterization of the separation of the enantiomers of citalopram, desmethylcitalopram and didesmethylcitalopram on an acetylated ß-cyclodextrin column, by use of two different chemometric programs - response surface modelling and sequential optimization was performed. Sequential optimization can be a quicker mean of optimizing a chromatographic separation; response surface modelling, in addition to enabling optimization of the chromatographic process, also serves as a tool for learning more about the separation mechanism. Studies of the antidepressant effect and pharmacokinetics of citalopram have been performed in adults, but the effects on children and adolescents have only been studied to a minor extent, despite the increasing use of citalopram in these age groups. A study was initiated to investigate adolescents treated for depression, with respect to the steady-state plasma concentrations of the enantiomers of citalopram and its demethylated metabolites. The ratios between the S- and R-enantiomers of citalopram and didesmethylcitalopram were in agreement with studies involving older patients. The concentrations of the S-(+)- and R-(-) enantiomers of citalopram and desmethylcitalopram were also in agreement with values from earlier studies. The results indicate that the use of oral contraceptives may have some influence on the metabolism of citalopram. This might be because of an interaction of the contraceptive hormones with the polymorphic CYP2C19 enzyme. Even though the SSRIs are considered less toxic compared with older monoamine-active drugs like the tricyclic/tetracyclic antidepressants, the risk of developing serious side effects such as ECG abnormalities and convulsions has been seen for citalopram, when larger doses have been ingested. Furthermore, fatal overdoses have been reported where citalopram alone was the cause of death. Data on the toxicity of each of the enantiomers in humans have not been reported and no data on blood levels of the enantiomers in cases of intoxication have been presented. An investigation was initiated on forensic autopsy cases where citalopram had been found at the routine screening and these cases were further analysed with enantioselective analysis to determine the blood concentrations of the enantiomers of citalopram and metabolites. Furthermore the genotyping regarding the polymorphic enzymes CYP2D6 and CYP2C19 were performed. In 53 autopsy cases, we found increasing S/R ratios with increasing concentrations of citalopram. We found also that high citalopram S/R ratio were associated with high parent drug to metabolite ratio and may be an indicator of recent intake. Only 3.8 % were found to be poor metabolizers regarding CYP2D6 and for CYP2C19 no poor metabolizer was found. Enantioselective analysis of citalopram and its metabolites can provide valuable information about the time that has elapsed between intake and death. Genotyping can be of help in specific cases but the possibility of pharmacokinetic interactions is apparently a far greater problem than genetic enzyme deficiency.On the day of the public defence the status of article IV was: Submitted.
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Oliveira, Elder Gonçalves de. "Desenvolvimento e validação de métodos analíticos para a análise enantiomérica da duloxetina e de sua impureza quiral em formulação farmacêutica." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2012. http://hdl.handle.net/10183/139442.
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A duloxetina é um potente inibidor duplo da recaptação de serotonina e norepinefrina, disponível como enantiômero puro, sob a forma S-duloxetina e comercializado como pellets em cápsulas. O R enantiômero da duloxetina é também um inibidor da recaptação, no entanto, este é menos potente que seu isômero, sendo considerado como impureza enantiomérica. Este trabalho teve como objetivos o desenvolvimento e a validação de métodos analíticos para o controle de qualidade da duloxetina e de sua respectiva impureza enantiomérica por cromatografia líquida de alta eficiência (CLAE), e por eletroforese capilar (EC). A resolução dos enantiômeros da duloxetina foi realizada a partir da utilização de fase estacionária quiral, baseada celulose, por CLAE. A separação por EC foi desenvolvida a partir da utilização de hidroxipropil-β-ciclodextrina (HPβCD) como seletor quiral. A validação dos métodos foi efetuada de acordo com os guias de validação disponíveis na literatura e os métodos propostos foram considerados específicos, lineares, precisos, exatos e robustos. A análise comparativa entre os métodos desenvolvidos demonstrou não haver diferença estatisticamente significativa na quantificação do enantiômero S-duloxetina.Duloxetine is a double potent inhibitor of serotonin and norepinephrine reuptake, available as a pure enantiomer, in the S-duloxetine form and marketed as pellets into capsules. The R enantiomer of duloxetine is also an inhibitor of reuptake, however, less potent and being considered enantiomeric impurity. This work aimed the development and validation of analytical methods for quality control of duloxetine and its respective enantiomeric impurity by high performance liquid chromatography (HPLC) and capillary electrophoresis (CE). The resolution of the enantiomers of duloxetine was performed with the use of chiral stationary phase, based on cellulose, by HPLC. The separation by CE was developed with the use of hydroxypropyl-β-cyclodextrin (HPβCD) as chiral selector. The method validation was performed according to the guides available in the literature and the proposed methods were considered specific, linear, precise, accurate and robust. The comparative analysis between the methods developed showed no statistically significant difference in the quantification of S-duloxetine enantiomer.