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

Zeruesenay Desta, Nadia V. Soukhova, Alan Morocho, Jae Park, Subena K. Mahal, David A. Flockhart

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

We have developed a simple, sensitive, specific and reproducible stereoselective high-performance liquid chromatography technique for analytical separation of cisapride enantiomers and measurement of cisapride enantiomers in human plasma. A chiral analytical column (ChiralCel OJ) was used with a mobile phase consisting of ethanol-hexane-diethylamine (35:64.5:0.5, v/v/v). This 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 for both cisapride enantiomers, while the limit of detection was 1 ng/ml. Intra- and inter-day C.V.s did not exceed 15% for all concentrations except at 12.5 ng/ml for EII (+)-cisapride, which was ~ 20 and 19%, respectively. The clinical utility of the method was demonstrated in a pharmacokinetic study of normal volunteers who received a 20 mg single oral dose of racemic cisapride. The preliminary pharmacokinetic data obtained using the method we describe here provide evidence for the first time that cisapride exhibits stereoselective disposition.

Original languageEnglish (US)
Pages (from-to)263-272
Number of pages10
JournalJournal of Chromatography B: Biomedical Sciences and Applications
Volume744
Issue number2
DOIs
StatePublished - Jul 21 2000

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Keywords

  • Cisapride

ASJC Scopus subject areas

  • Chemistry(all)

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