Abbreviations used: CYP2C8, cytochrome P450 2C8; GFZ, gemfibrozil; GFZ-d6, gemfibrozil-d6; GFZ-gluc, gemfibrozil 1-O-β-glucuronide; LC/MS, single quadrupole mass spectrometry; LC-MS/MS, tandem mass spectrometry; LLOQ, lower limit of quantification; OATP1B1, organic anion-transporting polypeptide 1B1.
Validation of an LC/MS method for the determination of gemfibrozil in human plasma and its application to a pharmacokinetic study
Article first published online: 15 NOV 2010
Copyright © 2010 John Wiley & Sons, Ltd.
Volume 24, Issue 12, pages 1300–1308, December 2010
How to Cite
Rower, J. E., Bushman, L. R., Hammond, K. P., Kadam, R. S. and Aquilante, C. L. (2010), Validation of an LC/MS method for the determination of gemfibrozil in human plasma and its application to a pharmacokinetic study. Biomed. Chromatogr., 24: 1300–1308. doi: 10.1002/bmc.1440
- Issue published online: 15 NOV 2010
- Article first published online: 15 NOV 2010
- Manuscript Accepted: 23 FEB 2010
- Manuscript Revised: 18 FEB 2010
- Manuscript Received: 6 JAN 2010
- human plasma
Gemfibrozil, a fibric acid hypolipidemic agent, is increasingly being used in clinical drug–drug interaction studies as an inhibitor of drug metabolizing enzymes and drug transporters. The validation of a fast, accurate and precise LC/MS method is described for the quantitative determination of gemfibrozil in an EDTA-anticoagulated human plasma matrix. Briefly, gemfibrozil was extracted from human plasma by an acetonitrile protein precipitation method. The assay was reproducible with intra-assay precision between 1.6 and 10.7%, and inter-assay precision ranging from 4.4 to 7.8%. The assay also showed good accuracy, with intra-assay concentrations within 85.6–108.7% of the expected value, and inter-assay concentrations within 89.4–104.0% of the expected value. The linear concentration range was between 0.5 and 50 µg/mL with a lower limit of quantitation of 0.5 µg/mL when 125 µL of plasma were extracted. This LC/MS method yielded a quick, simple and reliable protocol for determining gemfibrozil concentrations in plasma and is applicable to clinical pharmacokinetic studies. Copyright © 2010 John Wiley & Sons, Ltd.