title: A chiral LC-MS/MS method for the stereospecific determination of efonidipine in human plasma.
abstract: Efonidipine hydrochloride is a new generation dihydropyridine Ca(2+) channel blocker designed to inhibit both T-type and L-type Ca(2+) channels. Efonidipine possesses a chiral carbon and is clinically administered as a racemate. In the present study, an enantioselective and sensitive LC-MS/MS method of determining efonidipine enantiomers in human plasma was developed and validated to characterize the stereoselective pharmacokinetics. Plasma samples were processed by liquid-liquid extraction (LLE). Chiral separation was optimized on a CHIRALPAK(®) ID column using an isocratic mobile phase of acetonitrile/water (60:40, v/v). Detection was using MS in multiple reaction monitoring (MRM) mode, using the transitions of m/z 632.3→91.1 for efonidipine enantiomers, and m/z 493.3→117.2 for cilnidipine (internal standard). The calibration curves were linear over 0.100-20.0 ng/mL for each enantiomer. The lower limit of quantification (LLOQ) for each enantiomer was established at 0.100 ng/mL. Intra- and inter-day precisions were less than 12.1% for each enantiomer in terms of relative standard deviation (RSD), and accuracies were between -5.0% and 5.0% in terms of relative error (RE) for each enantiomer. No chiral inversion was observed during sample storage, preparation procedure and analysis. The validated method was successfully applied to a stereoselective pharmacokinetic study of efonidipine in healthy subjects after oral administration of 40 mg (20 mg × 2) efonidipine hydrochloride tablets.
authors: Department of Clinical Pharmacology, Aerospace Center Hospital, Beijing, PR China.
authors: Man
authors: M
authors: Liu
authors: Department of Clinical Pharmacology, Aerospace Center Hospital, Beijing, PR China.
authors: Ming
authors: M
authors: Deng
authors: Department of Clinical Pharmacology, Aerospace Center Hospital, Beijing, PR China.
authors: Dan
authors: D
authors: Zhang
authors: Department of Clinical Pharmacology, Aerospace Center Hospital, Beijing, PR China.
authors: Xiaolin
authors: X
authors: Wang
authors: Department of Clinical Pharmacology, Aerospace Center Hospital, Beijing, PR China.
authors: Jingyi
authors: J
authors: Ma
authors: Department of Clinical Pharmacology, Aerospace Center Hospital, Beijing, PR China.
authors: Hongna
authors: H
authors: Zhao
authors: Department of Clinical Pharmacology, Aerospace Center Hospital, Beijing, PR China.
authors: Lina
authors: L
authors: Zhang
authors: Department of Clinical Pharmacology, Aerospace Center Hospital, Beijing, PR China.
authors: Yang
authors: Y
authors: Tong
authors: Department of Clinical Pharmacology, Aerospace Center Hospital, Beijing, PR China. Electronic address: huichenliu@163.com.
authors: Huichen
authors: H
authors: Liu
mesh_terms: D000284:Administration, Oral; D002853:Chromatography, Liquid / Q000379:methods*; D004095:Dihydropyridines / Q000737:chemistry*; D006801:Humans; D059625:Liquid-Liquid Extraction / Q000379:methods; D009596:Nitrophenols / Q000737:chemistry*; D009943:Organophosphorus Compounds / Q000737:chemistry; D010949:Plasma / Q000737:chemistry*; D013237:Stereoisomerism; D013607:Tablets / Q000737:chemistry; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D004095:Dihydropyridines; D009596:Nitrophenols; D009943:Organophosphorus Compounds; D013607:Tablets; C066425:efonidipine; C065927:cilnidipine
keywords: Chiral; Efonidipine; Enantiomer; LC–MS/MS; Pharmacokinetics; Plasma