Simultaneous determination of ten antiarrhythic drugs and a metabolite in human plasma by liquid chromatography-tandem mass spectrometry

A simple, accurate and selective LC-MS/MS method was developed and validated for simultaneous quantification of ten antiarrhythic drugs (diltiazem, arniodarone, mexiletine, propranolol, sotalol, verapamil, bisoprolol, metoprolol, atenolol, carvedilol) and a metabolite (norverapamil) in human plasma. Plasma samples were simply pretreated with acetonitrile for deproteinization. Chromatographic separation was performed on a Capcell C-18 column (50 mm x 2.0 mm, 5 mu m) using a gradient mixture of acetonitrile and water (both containing 0.02% formic acid) as a mobile phase at flow rate of 0.3 ml/min. The analytes were protonated in the positive electrospray ionization (ESI) interface and detected in multiple reaction monitoring (MRM) mode. Calibration curves were linear over wide ranges from sub- to over-therapeutic concentration in plasma for all analytes. Intra- and inter-batch precision of analysis was < 12.0%, accuracy ranged from 90% to 110%, average recovery from 85.0% to 99.7%. The validated method was successfully applied to therapeutic drug monitoring (TDM) of antiarrhythic drugs in routine clinical practice. (c) 2006 Published by Elsevier B.V.