Enantioselective resolution and determination of racemic drugs using chiral high performance liquid chromatography and capillary electrophoresis

This dissertation deals with various aspects of chiral separations using chiral stationary phases in HPLC and various chiral selectors as background electrolyte additives in capillary zone electrophoresis (CZE). This was followed by the quantitation of mepivacaine and prilocaine enantiomers in biological fluids using both HPLC and HPCE.; In Chapter 1 the enantiomeric resolution of bupivacaine, prilocaine, mepivacaine and etidocaine was investigated using cellulose based stationary phases. The stationary phases studied were Chiralcel OD and Chiralcel OJ. Changes in mobile phase composition were investigated for their effect on the retention and resolution of the enantiomers.; In Chapter 2 the HPLC quantitation of R and S mepivacaine in human serum was developed. The method used solid phase extraction for sample cleanup. Chromatographic resolution was performed using a S-t-leucine, R-1-({dollar}alpha{dollar}-naphthyl) ethylamine stationary phase and a mobile phase of hexane-ethylene dichloride-absolute methanol (85:10:5, v/v/v). The flow rate was 0.8 ml/min and the analysis was performed at ambient temperature. The eluate was monitored by UV detection at 220 nm.; In Chapter 3, a stereoselective HPLC method was developed for the quantitation of prilocaine in human serum using solid phase extraction and UV detection. The method used a brush type stationary phase and the analytes were monitored at 220 nm.; In Chapter 4, a CZE method was developed for the quantitation of R(+) and S({dollar}-{dollar}) mepivacaine in human serum. The background electrolyte was a 100 mM phosphate buffer (pH 2.5) containing 20 mM of heptakis-(2,6-di-O-methyl)-{dollar}beta{dollar}-cyclodextrin and 30 nM of hexadecyltrimethyl ammonium bromide. A 72 cm uncoated fused silica capillary was used for the analysis. A liquid-liquid extraction was used to remove endogenous interferences. A comparison of the HPLC and CZE methods was performed with respect to various analytical figures of merit.; In Chapter 5, a CZE assay was developed for the stereoselective analysis of R and S prilocaine. The background electrolyte consisted of dimethyl cyclodextrin as the chiral selector. A 72 cm fused silica capillary was used for the analysis. The analytes were monitored using UV detection at 215 nm. A comparison of the HPLC and CE methods was performed with respect to reproducibility, limit of quantitation, theoretical plates and analysis times.; In Chapter 6, a CZE method for the enantioselective determination of S(+) and R({dollar}-{dollar}) ondansetron was developed using derivatized cyclodextrin-modified capillary electrophoresis. Solid phase extraction was used to remove endogenous materials. The method was highly selective and there was no interference from co-administered drugs.; In Chapter 7, a stereoselective resolution of ({dollar}pm{dollar}) DU 124884 was developed using free solution capillary electrophoresis with derivatized cyclodextrins as the chiral selector and micellar electrokinetic chromatography with sodium taurocholate as the chiral selector. The analytes were monitored at 254 nm.