Journal
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
Volume 48, Issue 4, Pages 1219-1224Publisher
ELSEVIER
DOI: 10.1016/j.jpba.2008.08.020
Keywords
Clopidogrel; Active metabolite; Thiol compound; 2-Bromo-3 '-methoxyacetophenone; LC-MS/MS; Pharmacokinetics
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A quantitative method for the determination of clopidogrel active metabolite (AM) in human plasma was developed and validated using liquid chromatography-tandem mass spectrometry (LC-MS/MS). clopidogrel AM contains a thiol group, thus requiring stabilization in biological samples. The alkylating reagent 2-bromo-3'-methoxyacetophenone was used to stabilize clopidogrel AM in blood. Ail analog of the derivatized clopidogrel AM Was Used as the internal standard (IS). The derivatized samples were subjected to solid-phase extraction with a C2 disk plate and the overall procedure exhibited good reaction (more than 90%) and recovery efficiencies (from 85% to 105%). The derivative of clopidogrel AM (MP-AM) and IS were separated on an ODS column and quantified by tandem mass spectrometry with electrospray ionization. No significant endogenous peaks corresponding to MP-AM or IS were detected ill blank human plasma samples, and no significant matrix effect was observed for MP-AM and IS in human plasma samples (from 102% to 121%). The calibration curve ranged from 0.5 to 250 ng/mL with good linearity, and extended by validation of a 50-fold dilution. In the intra- and inter-assay reproducibility tests, the accuracy and precision were within 12% relative error and 6% coefficient of variation, respectively. The derivatized MPAM was stable in human plasma for 4 months at -80 C. The validated method Was Successfully used to analyze clinical samples and determine the pharmacokinetics of clopidogrel AM. (C) 2008 Elsevier B.V. All rights reserved.
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