Enantiomeric HPLC and CE resolution and assay of selected drugs using chiral mobile phase additives and solid-phase extraction.

摘要

The dissertation discusses the resolution of selected drugs with reversed phase HPLC and CE using native and derivatized {dollar}beta{dollar}-cyclodextrins as chiral mobile phase additives and UV detection. The enantioseparation methods developed were validated in human serum using solid phase extraction.; In Chapter 1, native and derivatized {dollar}beta{dollar}-cyclodextrins were investigated as chiral mobile phase additives for the enantiomeric separation of selected drugs with reversed-phase columns. The chiral drugs investigated were oxazepam, temazepam, lorazepam, ketoprofen, fenoprofen, ibuprofen, chlorthalidone, terbutaline, trimeprazine and trimipramine. A new nonporous octadecylsilane column gave separations for most of the drugs.; In Chapter 2, a sensitive and stereospecific reversed phase HPLC method for the quantitation of ketoprofen enantiomers in human serum was developed with octadecylsilane solid phase extraction for serum sample clean-up. Chromatographic resolution of the ketoprofen enantiomers was performed on a nonporous octadecylsilane column with hydroxypropyl {dollar}beta{dollar}-cyclodextrin (HP-{dollar}beta{dollar}-CD) as the mobile phase additive.; In Chapter 3, a stereoselective reversed phase HPLC method was developed and validated for the analysis of the enantiomers of trimipramine in human serum. The assay used octadecylsilane solid phase extraction for serum sample clean-up and was free of interference from desmethyl-trimipramine, 2-hydroxy-desmethyl-trimipramine and 2-hydroxy-trimipramine, the three major chiral metabolites of trimipramine.; In Chapter 4, the HPLC quantitation of ({dollar}-{dollar}) and (+) pentazocine in human serum was developed with phenyl solid phase extraction as the sample clean-up technique. Chromatographic resolution of the pentazocine enantiomers was performed on a octadecylsilane column with sulfated-{dollar}beta{dollar}-cyclodextrin as the chiral mobile phase additive.; In Chapter 5, a capillary zone electrophoresis assay for the enantioselective determination of ({dollar}-{dollar}) and (+) pentazocine in human serum was developed with phenyl solid phase extraction as the sample clean-up technique. Resolution of the pentazocine enantiomers was achieved using methyl-{dollar}beta{dollar}-cyclodextrin (Me-{dollar}beta{dollar}-CD) in 100mM phosphate buffer pH 2.5 with an uncoated fused silica capillary.; In Chapter 6, a novel and rapid HPLC method for the separation and determination of R({dollar}-{dollar}) and S(+) apomorphine in serum was developed. The method used an octasilane solid phase extraction column for sample clean-up and the chiral column used was a cellulose-based chiral column (Chiralcel OD-R).