DETERMINATION OF CISAPRIDE IN HUMAN PLASMA BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY

An HPLC method has been developed for the quantification of cisapride in plasma for pharmacokinetic studies. Clebopride was used as internal standard. Plasma samples were extracted at alkaline pH with tert-buty l methyl ether. The organic phase was then extracted with sulphuric ac id to eliminate endogenous interferences, and cisapride and the intern al standard were then extracted at alkaline pH into tert-butyl methyl ether. After evaporation of tert-butyl methyl ether, the residue was a nalysed by HPLC, Chromatography was performed at 20 degrees C on a 250 mm x 4 mm i.d. reversed-phase column selective for basic compounds. T he isocratic mobile phase was 48:52 (v/v) acetonitrile-water containin g 0.05 M potassium dihydrogen phosphate and 0.04 M triethylamine, adju sted to pH 5.5; the flow rate was 1 mL min(-1). Cisapride and the inte rnal standard were detected by ultraviolet monitoring at 276 nm. The c alibration graph was linear for quantities of cisapride from 1 to 200 ng mL(-1). Intra- and inter-day precision (CV) did not exceed 13.98%. The limit of quantitation (LOQ) was 0.68 ng mL(-1) for human plasma. T he applicability of the method has been demonstrated in a pharmacokine tic study of normal volunteers who received 10 mg cisapride orally.