Stereospecific resolution and quantitation of selected pharmaceuticals on reversed phase chiral stationary phases and solid phase extraction

This dissertation discusses the resolution of selected pharmaceuticals on HPLC chiral stationary phases such as cellulose derivatives, crown ethers, proteins, and beta-cyclodextrin and their derivatives. Stereospecific methods for the quantitation of selected pharmaceuticals in human serum were also developed and validated using two reversed phase cellulose based chiral stationary phases (a Chiralcel OD-R or Chiralcel OJ-R column), UV detection and solid phase extraction.; In Chapter 1, several strategies for the HPLC analysis of chiral drugs in the USP 23 compendial monographs are proposed based on the data obtained from a literature survey and additional experiments in our laboratory using reversed phase chiral stationary phases and conventional reversed-phase columns with addition of chiral selectors to the mobile phase.; In Chapter 2, a reversed-phase HPLC method was developed for the simultaneous separation of diazepam and its achiral (nordiazepam) and chiral (oxazepam and temazepam) metabolites in human serum. A disc solid phase extraction method was developed for the investigation of recoveries of diazepam, nordiazepam, and enantiomers of oxazepam and temazepam in human serum.; In Chapter 3, a sensitive HPLC method for the quantitation of praziquantel enantiomers in human serum was developed and validated. The method involves the use of a novel disc solid-phase extraction for sample clean-up prior to HPLC analysis and is also free of interference from trans-4-hydroxypraziquantel, the major metabolite of praziquantel. Recovery, intra-day and inter-day precision, intra-day and inter-day accuracy, and linear calibration curve data were provided for both enantiomers.; In Chapter 4, a liquid chromatographic method was developed for the assay of R(+)-and S({dollar}-{dollar})-promethazine enantiomers in human serum. A novel mixed mode disc solid-phase extraction method was developed and optimized for sample clean-up. The method was validated in terms of recovery, inter-day and intra-day accuracy and precision as well as linear calibration curve for both enantiomers.; In Chapter 5, a sensitive and stereospecific method for the quantitation of trimipramine enantiomers in human serum was developed and validated. The assay involves the use of a novel mixed-mode solid-phase extraction for serum sample clean-up and is also free of interference from desmethyl-trimipramine, 2-hydroxy-trimipramine, and 2-hydroxy-desmethyl-trimipramine, the three major metabolites of trimipramine. Recovery, inter-day and intra-day accuracy and precision as well as linear calibration curve data were provided for both enantiomers. In addition, separation of the metabolite enantiomers were investigated.; In Chapter 6, a stereospecific HPLC method was developed/validated for the assay of R({dollar}-{dollar})- and S(+)-ondansetron enantiomers in human serum. Limit of detection and limit of quantitation are discussed. A cartridge solid phase extraction method was used for the quantitative recovery of R- and S-ondansetron enantiomers in human serum.