BIO ANALYTICAL LIQUID CHROMATOGRAPHIC DETERMINATION OF SOME SELECTED CHIRAL DRUGS IN PHARMACEUTICAL DOSAGE FORMS

Abstract

quot(Bio-analytical liquid chromatographic determination of some newlineselected chiral drugs in pharmaceutical dosage forms) newline newlineOBJECTIVE: The main objective of the study is to develop simple and reproducible analytical and bio analytical methods for the enantiomer separation of three selected anti-histamine drugs followed by their application for the determination of stereo-selective pharmacokinetics in rabbits. newlineMETHODOLOGY: Doxylamine, Carbinoxamine and Hydroxyzine enantiomers were resolved in reverse/normal phase liquid chromatography. These enantiomers were administered to rabbit. The blood samples were withdrawn at different time intervals and the concentration of (R)- and (S)- enantiomers was analysed by the optimized UFLC method. newlineRESULTS: The separation of doxylamine optical isomers and internal standard was achieved within 15 min run time. The study in rabbits showed higher plasma concentrations of (d)- doxylamine compared with (l)- form in rabbits. Separation of pargaverine hydrochloride (IS), (d)- and (l)-carbinoxamine enantiomers was achieved at 4.8, 5.6 and 6.3 min respectively. Both the carbinoxamine enantiomers produced linear curves between 20 7500ng/mL in plasma. The study in rabbits showed higher plasma concentrations of (l)- carbinoxamine compared with (d)- form in rabbits. Separation of cyclizine hydrochloride (IS), (S)- and (R)- hydroxyzine enantiomers was achieved at 5.7, 10.2 and 11.1 min respectively. Calibration curves were linear for both hydroxyzine enantiomers between 20 1000 ng/mL concentrations in plasma. Kinetic study in rabbits showed almost same plasma concentrations of both (R)- and (S)- hydroxyzine enantiomers. newlineCONCLUSION: The developed UFLC methods of all the three antihistamine drugs were validated and used to determine the pharmacokinetics in experimental rabbits. The In-vivo study in rabbits showed a stereo-selective disposition of enantiomers between (d)- and (l)- enantiomers of doxylamine and carbinoxamine in rabbits. But, the stereoselective disposition was not observed between (R)-