Simultaneous determination of aceclofenac and its three metabolites in plasma using liquid chromatography-tandem mass spectrometry

초록

A new LC/MS/MS-based method allows simultaneous determination of aceclofenac and its three metabolites (4'-OH-aceclofenac, diclofenac, and 4'-OH-diclofenac) in plasma. After acetonitrile-induced precipitation of proteins from the plasma samples, aceclofenac, 4'-OH-aceclofenac, diclofenac, 4'-OH-diclofenac, and flufenamic acid (an internal standard) were chromatographed on a reverse-phase C-18 analytical column. The isocratic mobile phase of acetonitrile/0.1% formic acid((aq)) [80:20 (v/v)] was eluted at 0.2 mL/min. Quantification was performed on a triple-duadrupole mass spectrometer employing electrospray ionization, and the ion transitions were monitored in multiple reaction-monitoring mode. The monitored transitions for aceclofenac, diclofenac, 4'-OH-diclofenac, 4'-OH-aceclofenac and flufenamic acid were m/z 352.9 -> 74.9, 296.1 -> 251.7, 311.8 -> 267.7, 368.9 -> 74.9, and 279.9 -> 235.9, respectively. The coefficient of variation of the assay precision was less than 6.5%, and the accuracy ranged from 93% to 103%. The limits of detection were 2 ng/mL for aceclofenac and 0.2 ng/mL for both diclofenac and 4'-OH-diclofenac. This method was used successfully to measure the concentrations of aceclofenac and its three metabolites in plasma from healthy subjects after administration of a single 100-mg oral dose of aceclofenac. This analytic method is a very simple, sensitive, and accurate way to determine the pharmacokinetics of aceclofenac and its metabolites. (c) 2007 Published by Elsevier B.V.

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