Determination of the enantiomers of nisoldipine in human plasma using high-performance liquid chromatography on a chiral stationary phase and gas chromatography with mass-selective detection

Abstract

A method is described that combines chiral HPLC and off-line GC with mass-selective detection for the quantitation of the enantiomers of nisoldipine [(±)-I] in human plasma. An isotope-labelled internal standard [nine-fold deuterated (±)-I] is used throughout the assay. The limit of quantification is 0.1 μg/l for each enantiomer. Data on the precision, accuracy and selectivity of the method are presented. Enantioselective analysis was performed in subjects receiving the racemic drug in tablet form. In healthy volunteers the maximum concentration and the area under the curve of the pharmacologically more active (+)-enantiomer were greater by 9-fold and 13-fold, respectively, compared to those of the (−)-enantiomer. In elderly hypertensive patients plasma concentrations 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 differences between the plasma concentrations of the enantiomers.