Determination of Manidipine in Human Plasma by UPLC-MS/MS and its Application to a Bioequivalence Study

Abstract

A rapid and highly sensitive method for the quantification of manidipine in human plasma was developed. Cleanup utilizing a 96-well solid-phase extraction technique is a simple and high-throughput method for extracting both manidipine and its internal standard felodipine from the quality-control samples: 97.5 +/- 2.1% for manidipine and 95.6 +/- 2.5% for IS. The ultra-performance liquid chromatography (UPLC) with tandem mass spectrometry (MS/MS) analytical tool, operated in a selective reaction monitoring mode was validated for manidipine quantification. The limit of detection and the lower limit of quantification were found to be 0.03 and 0.07 ng/mL, respectively. The intra-and inter-day precision was <3%, and accuracies ranged from 93.6 to 98.3%. A combination of the high-throughput SPE cleanup, and the sensitive and robust UPLC-MS/MS detection of manidipine at the picogram level was successfully applied to a bioequivalence study; T-max, C-max, and AUC(0-12) obtained from reference tablet were averaged at 2.26 h, 5.78 ng/mL, and 20.82 ng h/mL, whereas those from test one were at 2.31 h, 5.64 ng/mL, and 21.37 ng h/mL, respectively.