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

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 x 2.1 mm, 5 mu m) 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 mu g 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.