Analysis of benidipine enantiomers in human plasma by liquid chromatography–mass spectrometry using a macrocyclic antibiotic (Vancomycin) chiral stationary phase column

• Published in: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Analytical technologies in the biomedical and life sciences, 2005-01, Vol.814 (1), p.75-81
• Main Authors: Kang, Wonku, Lee, Dong-Jun, Liu, Kwang-Hyeon, Sunwoo, Yu Eun, Kwon, Kwang-il, Cha, In-June, Shin, Jae-Gook
• Format: Article
• Language: English
• Subjects: Analysis; Analytical, structural and metabolic biochemistry; Benidipine; Biological and medical sciences; Calcium Channel Blockers - blood; Calcium Channel Blockers - chemistry; Calcium Channel Blockers - pharmacokinetics; Chiral stationary phase; Chromatography, Liquid - instrumentation; Chromatography, Liquid - methods; Dihydropyridines - blood; Dihydropyridines - chemistry; Dihydropyridines - pharmacokinetics; Enantiomers; Fundamental and applied biological sciences. Psychology; General pharmacology; Humans; Medical sciences; Pharmacology. Drug treatments; Reference Values; Reproducibility of Results; Sensitivity and Specificity; Stereoisomerism; Tandem mass spectrometry
• ISSN: 1570-0232; 1873-376X
• DOI: 10.1016/j.jchromb.2004.10.006

We used a novel chromatographic method to rapidly and simply characterize the pharmacokinetics of benidipine enantiomers in human plasma. The stereoisomers of benidipine were extracted from plasma using diethylether under alkaline conditions. After evaporating the organic layer, the residue was reconstituted in the mobile phase (methanol:acetic acid:triethylamine, 100:0.01:0.0001, v/v/v). The enantiomers in the extract were separated on a macrocyclic antibiotic (Vancomycin) chiral stationary phase column. The mobile phase was eluted at 1 ml/min and was split by an interface. One-fifth of the eluent was used to quantify both isomers in a tandem mass spectrometer in multiple reaction-monitoring mode. The coefficient of variation of the precision of the assay was less than 8%, the assay accuracy was between 93.4 and 113.3%, and the limit of detection was 0.05 ng/ml for 1 ml of plasma. The method described above was used to measure the concentration of both benidipine enantiomers in plasma from healthy subjects who received a single oral dose of a racemate of 8 mg benidipine. The C max and AUC inf values of (+)-alpha benidipine were higher than those of (−)-alpha benidipine by 1.96- and 1.85-fold, respectively ( p < 0.001), whereas, the T max and t 1/2 for each of the benidipine stereoisomers were not significantly different.