Enantioselective assay for the determination of nisoldipine in dog, rat and mouse plasma by chiral microbore high-performance liquid chromatography combined with gas chromatography-mass spectrometry.
A sensitive, selective and validated method for the enantioselective determination of (+)- and (-)-nisoldipine in rat, mouse and dog plasma following administration of nisoldipine racemate is described. The alkalized plasma samples containing [13C4]nisoldipine racemate as internal standard (ISTD) were extracted once with toluene. The enantiomers of nisoldipine were quantitatively separated by high-performance liquid chromatography on a 250 x 2 mm I.D. column containing tris(4-methylbenzoate)-modified cellulose on silica. The fractions containing either the (+) or (-)-enantiomer of the analyte and [13C4]ISTD were analysed by gas chromatography with mass-selective detection in the single-ion monitoring mode. The limits of determination and detection were 0.5 and 0.2 ng/ml, respectively, the total precision was better than 7% (R.S.D. at 5 and 50 ng/ml, n = 35) and the accuracy was better than 10% (0.5-100 ng/ml, n = 23). The sum of the concentrations of the enantiomers determined with this assay corresponds to the concentration of the racemate determined independently by capillary gas chromatography with electron-capture detection (accuracy better than 15%, 1-80 ng/ml). The method was used for the analysis of more than 500 plasma samples obtained from toxicokinetic studies.
Zimmer
D
D
Institute of Pharmacokinetics, Pharma Research Centre, Bayer AG, Wuppertal, Germany.
Muschalek
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V
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000706:statistics & numerical data; D004285:Dogs; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D007700:Kinetics; D008297:Male; D051379:Mice; D015737:Nisoldipine / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D012680:Sensitivity and Specificity; D013237:Stereoisomerism
D015737:Nisoldipine