Determination of Revaprazan in Human Plasma by LC–MS–MS and Application to a Pharmacokinetic Study in Chinese Volunteers

Abstract

A sensitive, specific, and rapid liquid chromatography–electrospray ionization–tandem mass spectrometry (LC–ESI–MS–MS) method was developed for determination of revaprazan in human plasma. Plasma samples were simply treated with methanol to precipitate, and then isolated supernatants were directly injected into the LC–ESI–MS–MS system. A Thermo Hypurity C18 column (150 × 2.1 mm, 5 μm) with mobile phase of methanol–water (70:30, v/v) containing 0.05% formic acid was used for chromatographic separation. Mass-spectrometric quantification was carried out in multiple reaction monitoring (MRM) mode, monitoring the m/z transitions 363.1 → 245.1 for revaprazan and 531.2 → 489.2 for ketoconazole (internal standard, IS) in positive ion mode. The linear calibration curves covered a concentration range of 2–1,000 μg L−1. The intra- and interday precisions (percentage relative standard deviation, RSD%) for revaprazan at three quality control levels were all <5%, and the accuracies were between 90% and 110%. The method has been successfully applied to a pharmacokinetic study involving 12 Chinese volunteers, and the main pharmacokinetic parameters of revaprazan in Chinese population are reported for the first time.