Analysis of benidipine enantiomers in human plasma by liquid chromatography-mass spectrometry using a macrocyclic antibiotic (Vancomycin) chiral stationary phase column.
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.
Kang
Wonku
W
Department of Pharmacology and Pharmacogenomics Research Center, College of Medicine, Inje University, Busan 614-735, Republic of Korea.
Lee
Dong-Jun
DJ
Liu
Kwang-Hyeon
KH
Sunwoo
Yu Eun
YE
Kwon
Kwang-il
KI
Cha
In-June
IJ
Shin
Jae-Gook
JG
D002121:Calcium Channel Blockers / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D002853:Chromatography, Liquid / Q000295:instrumentation / Q000379:methods*; D004095:Dihydropyridines / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D012016:Reference Values; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013237:Stereoisomerism
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C061004:benidipine