DETERMINATION OF THE ENANTIOMERS OF NISOLDIPINE IN HUMAN PLASMA USINGHIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY ON A CHIRAL STATIONARY-PHASE AND GAS-CHROMATOGRAPHY WITH MASS-SELECTIVE DETECTION

A method is described that combines chiral HPLC and off-line GC with m ass-selective detection for the quantitation of the enantiomers of nis oldipine [(+)-I] in human plasma. An isotope-labelled internal standar d [nine-fold deuterated (+/-)-I] is used throughout the assay. The lim it of quantification is 0.1 mu g/l for each enantiomer. Data on the pr ecision, accuracy and selectivity of the method are presented. Enantio selective analysis was performed in subjects receiving the racemic dru g in tablet form. In healthy volunteers the maximum concentration and the area under the curve of the pharmacologically more active (+)-enan tiomer were greater by 9-fold and 13-fold, respectively, compared to t hose of the (-)-enantiomer. In elderly hypertensive patients plasma co ncentrations of (+)-I were ca. five times as high as those of the (-)- enantiomer. Stereoselectivity was not affected by hepatic impairment. After intravenous administration of (+/-)-I there were no relevant dif ferences between the plasma concentrations of the enantiomers.