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, amiodarone, 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 (50mmx2.0mm, 5microm) using a gradient mixture of acetonitrile and water (both containing 0.02% formic acid) as a mobile phase at flow rate of 0.3ml/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.
Li
Shuijun
S
Central Laboratory, Shanghai Xuhui Central Hospital, Shanghai 200031, China.
Liu
Gangyi
G
Jia
Jingying
J
Liu
Yun
Y
Pan
Cheng
C
Yu
Chen
C
Cai
Yongbao
Y
Ren
Jianying
J
D000638:Amiodarone / Q000097:blood / Q000737:chemistry; D000889:Anti-Arrhythmia Agents / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D001262:Atenolol / Q000097:blood / Q000737:chemistry; D017298:Bisoprolol / Q000097:blood / Q000737:chemistry; D002227:Carbazoles / Q000097:blood / Q000737:chemistry; D000077261:Carvedilol; D002853:Chromatography, Liquid / Q000379:methods*; D004110:Diltiazem / Q000097:blood / Q000737:chemistry; D006801:Humans; D008790:Metoprolol / Q000097:blood / Q000737:chemistry; D008801:Mexiletine / Q000097:blood / Q000737:chemistry; D015394:Molecular Structure; D011412:Propanolamines / Q000097:blood / Q000737:chemistry; D011433:Propranolol / Q000097:blood / Q000737:chemistry; D015203:Reproducibility of Results; D013015:Sotalol / Q000097:blood / Q000737:chemistry; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014700:Verapamil / Q000031:analogs & derivatives / Q000097:blood / Q000737:chemistry / Q000378:metabolism
D000889:Anti-Arrhythmia Agents; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D008801:Mexiletine; D001262:Atenolol; C016904:norverapamil; D011433:Propranolol; D013015:Sotalol; D014700:Verapamil; D004110:Diltiazem; D008790:Metoprolol; D000638:Amiodarone; D017298:Bisoprolol