A Sensitive and Reliable Method for the Determination of Ezetimibe by LC-MS/MS and its Application to a Pharmacokinetic Study in Healthy Chinese Volunteers

In this study, a selective and reliable high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantitative analysis of ezetimibe (EZE) was developed, validated and subsequently employed in a pharmacokinetic research of EZE in healthy Chinese subject after single 10 mg oral dose of EZE tablets (Zetia@). EZE was extracted from plasma by liquid-liquid extraction (LLE) using methyl tert-butyl ether and detected by LC-MS/MS with lower limit of quantitation of 0.1001 ng/mL. Chromatographic separation of analyte was achieved on a Hedera ODS-2 column using mobile phase that consisted of acetonitrile-water with gradient elution. Quantification was conducted using an electrospray ionization (ESI) source in negative ion mode with multiple reaction monitoring (MRM) transitions of mlz 408.5 -> 2713 for EZE and mlz 364.0 -> 188.9 for indapamide (internal standard, IS). This method exhibited satisfactory linearity, accuracy, precision, matrix effect, extraction recovery and stability, which was found to be suitable for supporting pharmacokinetic and bioequivalence studies of EZE.