Determination of (+)- and (-)-nilvadipine in human plasma using chiral stationary-phase liquid chromatography and gas chromatography-mass spectrometry, and a preliminary pharmacokinetic study in humans.
A stereoselective and sensitive method for the determination of nilvadipine, a new dihydropyridine calcium antagonist, in human plasma was developed. An internal standard, the deuterated analogue of racemic nilvadipine, was added to the plasma and extracted with an n-hexane:ethyl acetate (92.5:7.5) mixture under alkaline conditions. Each enantiomer in the extract was separated on a chiral stationary-phase column (Chiralpak OT(+)) for HPLC, and the effluents containing the respective isomers were collected. Each effluent was analyzed by fused-silica capillary column GC-electron capture negative ion chemical ionization MS. The mass spectrometer was set to monitor the molecular anions of nilvadipine and the internal standard. Calibration curves were linear for concentrations of each enantiomer from 0.025 to 10 ng/mL. The mean intra- and interassay precisions, as estimated by RSD, were less than 6% for each enantiomer. Assay suitability was assessed in a pharmacokinetic study in which four subjects were given a 6-mg oral dose of racemic nilvadipine. The t1/2 values of the two enantiomers were similar, but the AUC values of the more potent (+)-enantiomer were 2.4-3.6 times higher than those of its optical antipode.
D000328:Adult; D002121:Calcium Channel Blockers / Q000097:blood*; D002853:Chromatography, Liquid; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007700:Kinetics; D008297:Male; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000097:blood; D013237:Stereoisomerism
D002121:Calcium Channel Blockers; C035100:nilvadipine; D009543:Nifedipine