Stereoselective determination of cisapride, a prokinetic agent, in human plasma by chiral high-performance liquid chromatography with ultraviolet detection: application to pharmacokinetic study

We have developed a simple, sensitive, specific and reproducible stereosele ctive high-performance liquid chromatography technique for analytical separ ation of cisapride enantiomers and measurement of cisapride enantiomers in human plasma. A chiral analytical column (ChiralCel OJ) was used with a mob ile phase consisting of ethanol-hexane-diethylamine (35:64.5:0.5, v/v/v). T his assay method was Linear over a range of concentrations (5-125 ng/ml) of each enantiomer. The limit of quantification was 5 ng/ml in human plasma f or both cisapride enantiomers, while the limit of detection was 1 ng/ml. In tra- and inter-day C.V.s did not exceed 15% for all concentrations except a t 12.5 ng/ml for EII (+)-cisapride, which was similar to 20 and 19%, respec tively. The clinical utility of the method was demonstrated in a pharmacoki netic study of normal volunteers who received a 20 mg single oral dose of r acemic cisapride. The preliminary pharmacokinetic data obtained using the m ethod we describe here provide evidence for the first time that cisapride e xhibits stereoselective disposition. (C) 2000 Elsevier Science B.V. All rig hts reserved.