A chiral LC-MS/MS method for the stereospecific determination of efonidipine in human plasma

作者：Liu, Man; Deng, Ming; Zhang, Dan; Wang, Xiaolin; Ma, Jingyi; Zhao, Hongna; Zhang, Lina; Tong, Yang; Liu, Huichen^*

来源：Journal of Pharmaceutical and Biomedical Analysis, 2016, 122: 35-41.

DOI：10.1016/j.jpba.2016.01.039

• Efonidipine
• Enantiomer
• Chiral
• Plasma
• LC-MS/MS
• Pharmacokinetics

Efonidipine hydrochloride is a new generation dihydropyridine Ca2+ channel blocker designed to inhibit both T-type and L-type Ca2+ 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 (R) 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 6323 -> 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 x 2) efonidipine hydrochloride tablets.

• 出版日期2016-4-15
• 单位航天中心医院