Determination of the novel antiarrhythmic drug sulcardine sulfate in human plasma by liquid chromatography tandem-mass spectrometry and its application inthe clinical pharmacokinetic study.

Sulcardine sulfate (Sul), a novel antiarrhythmic agent, is currently in phase I and phase II clinical trials. To elucidate its clinical pharmacokinetic characteristics, a rapid and accurate liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the quantification of Sul in human plasma. Plasma samples were precipitated by acetonitrile and isotope-labeled sulcardine was added as internal standard. The analysis was carried out on a Capcell Pak C-18 MG III column (100x2.0mm, 5m) with 0.1% formic acid in acetonitrile solution and water (17:83, v/v) as mobile phase. The linear range was 5.0-1000ng/mL for Sul, with a lower limit of quantification of 5.0ng/mL. The intra- and inter-batch CVs were within +/- 11.0% and the accuracies were 4.9-107.3%. Our method, for the first time, allows the rapid (only 3.0min) and accurate quantification of Sul in human plasma. The method has been successfully applied in the pharmacokinetic study of Sul in a clinical trial following oral administration of Sul to healthy volunteers. Copyright (c) 2016 John Wiley & Sons, Ltd.