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 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 approximately 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.
Desta
Z
Z
Department of Medicine, Georgetown University Medical Center, Washington, DC 20007, USA. gebreegz@gusun.georgetown.edu
Soukhova
N V
NV
Morocho
A
A
Park
J
J
Mahal
S K
SK
Flockhart
D A
DA
D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D020117:Cisapride / Q000097:blood* / Q000493:pharmacokinetics; D005260:Female; D005765:Gastrointestinal Agents / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D012016:Reference Values; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism
D005765:Gastrointestinal Agents; D020117:Cisapride