Validation of an LC/MS method for the determination of gemfibrozil in human plasma and its application to a pharmacokinetic study

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.