Development of a sensitive liquid chromatography/tandem mass spectrometry method for the determination of fenofibric acid in rat plasma

A rapid and sensitive LC-MS/MS method for the quantification of fenofibric acid in rat plasma was developed and validated. Plasma samples were prepared by liquidliquid extraction with a mixture of N-hexanedichloromethaneisopropanol (100:50:5, v/v/v). Isocratic chromatographic separation was performed on a reversed-phase Discovery C18 column (2.1?x?50?mm, 5?mu m). The mobile phase was methanolwaterformic (75:25:0.25, v/v/v). Detection of fenofibric acid and the internal standard (IS) diclofenac acid was achieved by ESI MS/MS in the negative ion mode using m/z 317???m/z 213 and m/z 294???m/z 250 transitions, respectively. The method was linear from 0.005 to 1.250?mu g/mL when 100 mu L plasma was analyzed. The lower limit of quantification was 0.005?mu g/mL. The intra- and inter-day precision values were below 8.2%, and accuracy ranged from -0.9 to 2.1% in all quality control samples. The recovery was 90.394.7% and 83.3% for fenofibric acid and IS, respectively. Total run time for each sample analysis was 2.5?min. The validated method was successfully applied to a pharmacokinetic study in six rats after oral administration of fenofibrate, the ester prodrug of fenofibric acid (equivalent to fenofibric acid 5?mg/kg). The method permits laboratory scientists with access to the appropriate instrumentation to perform rapid fenofibric acid determination. Copyright (c) 2011 John Wiley & Sons, Ltd.