Part I. Rapid analysis of pharmaceutical compounds using high-speed HPLC columns. Part II. Simulataneous determination of drugs in tablet dosage forms using packed column supercritical fluid chromatography. Part III. Pharmaceutical analysis of selected drugs using capillary electrophoresis.

摘要

Part I of this dissertation describes the use of high speed HPLC columns: Alltech Rocket Alltima C 18, Micra NPS ODS-I, and HP Zorbax SB-C18, for separations of selected drug mixtures. The high speed resolution without loss of efficiency resulted from the use of short column lengths and small-size particles.; In Chapter I, two drug combinations, codeine-guaifenesin and acetaminophen-caffeine, were investigated on three high speed columns. Baseline separations were achieved with all columns under 4 min. Intra- and inter-day RSD, limits of detection, retention factors, theoretical plates, tailing factors, selectivity values, and resolutions were calculated for the separated drugs.; In Chapter II, methods are presented using high speed columns for three selected analyte mixtures, theophylline-guaifenesin, acetaminophen-codeine, and hydrochlorothiazide-propranolol. The performance of each column was compared by studying different chromatographic parameters.; In Part II of this dissertation, packed column supercritical fluid chromatography (SFC) is used in the various applications of pharmaceutical analysis.; Chapter III describes an isobaric and isothermal separation of a trimethoprim and sulfamethoxazole mixture using packed column SFC.; In Chapter IV, a SFC separation method for a chlordiazepoxide and amitriptyline mixture is described. Part III of this dissertation presents pharmaceutical analysis applications of selected drugs using capillary electrophoresis (CE).; In Chapter V, a micellar electrokinetic capillary chromatography (MEKC) method was developed for the simultaneous determination of a trimethoprim and sulfamethoxazole mixture in bulk and tablet dosage forms.; In Chapter VI, an amitriptyline and chlordiazepoxide mixture was quantified in bulk and tablet dosage forms by a capillary zone electrophoresis (CZE) method.; In Chapter VII, the D and L enantiomers of vesamicol were resolved using sulfated-β-cyclodextrin (S-β-CD) in CE. The effects of various factors such as cyclodextrin (CD) type, CD concentration, buffer type, buffer concentration, and pH on the enantioseparations were investigated.; In Chapter VIII, a chiral CE method for nomifensine, a dopamine uptake blocker, in human serum samples is described. The Bond Elut C 18 cartridges were used for solid phase extraction (SPE) of nomifensine serum samples with absolute recoveries in excess of 95% for the enantiomers. The limits of detection (LODs) (S/N = 3) were 0.5 μg/ml for both enantiomers at 210 nm. Calibration curves were obtained using an internal standard method with regression coefficients greater than 0.991 (n = 15).