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

J Chromatogr B Analyt Technol Biomed Life Sci. 2007 Mar 1;847(2):174-81. doi: 10.1016/j.jchromb.2006.10.013. Epub 2006 Nov 20.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amiodarone / blood
  • Amiodarone / chemistry
  • Anti-Arrhythmia Agents / blood*
  • Anti-Arrhythmia Agents / chemistry
  • Anti-Arrhythmia Agents / metabolism
  • Atenolol / blood
  • Atenolol / chemistry
  • Bisoprolol / blood
  • Bisoprolol / chemistry
  • Carbazoles / blood
  • Carbazoles / chemistry
  • Carvedilol
  • Chromatography, Liquid / methods*
  • Diltiazem / blood
  • Diltiazem / chemistry
  • Humans
  • Metoprolol / blood
  • Metoprolol / chemistry
  • Mexiletine / blood
  • Mexiletine / chemistry
  • Molecular Structure
  • Propanolamines / blood
  • Propanolamines / chemistry
  • Propranolol / blood
  • Propranolol / chemistry
  • Reproducibility of Results
  • Sotalol / blood
  • Sotalol / chemistry
  • Tandem Mass Spectrometry / methods*
  • Verapamil / analogs & derivatives
  • Verapamil / blood
  • Verapamil / chemistry
  • Verapamil / metabolism

Substances

  • Anti-Arrhythmia Agents
  • Carbazoles
  • Propanolamines
  • Carvedilol
  • Mexiletine
  • Atenolol
  • norverapamil
  • Propranolol
  • Sotalol
  • Verapamil
  • Diltiazem
  • Metoprolol
  • Amiodarone
  • Bisoprolol