Development of a selective and fast LC-MS/MS for determination of WSJ-537, an xanthine oxidase inhibitor, in rat plasma: Application to a pharmacokinetic study.

Abstract Gout is a common metabolic disorder caused by the deposition of monosodium urate crystals within joints. A new kind of xanthine oxidase inhibitor, WSJ-537, was developed as a potential drug. In order to investigate the pharmacokinetic behavior in vivo , a liquid chromatography-tandem mass spectrometry (LC–MS/MS) method for determination the concentration of WSJ-537 in rat plasma was developed. After extraction by protein precipitation method with acetonitrile, the chromatographic separation was accomplished on a Venusil ASB C 18 column(2.1 mm × 50 mm, 3 mm)at a flow rate of 0.3 mL min −1 with the mobile phase consisting of acetonitrile-ammonium acetate (33:67, v/v ). An electrospray ionization (ESI) source was applied and operated in the positive ion mode. The plasma concentration was detected by multiple reactions monitoring (MRM) mode with the target fragment ions m / z 410.2 →  m / z 368.1 for WSJ-537 and m / z 244.1 →  m / z 185.0 for the IS. Good linearity was observed in the range of 20–800 ng mL −1 (r = 0.9947). The recovery of WSJ-537 in rats plasma was more than 85%. This method was suitable for pharmacokinetic studies after oral administration of 10 mg/kg WSJ-537 in rats.