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.
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 C18 column(2.1mm×50mm, 3mm)at a flow rate of 0.3mLmin(-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 20-800ngmL(-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 10mg/kg WSJ-537 in rats.
Department of Pharmacy, The First Hospital of China Medical University, Nanjing Street No.155, Heping District, Shenyang City 110001, China. Electronic address: linjianyangydyy@126.com.
Jianyang
J
Lin
Department of Pharmacy, The First Hospital of China Medical University, Nanjing Street No.155, Heping District, Shenyang City 110001, China.
Tian
T
Yang
Department of Pharmacy, The First Hospital of China Medical University, Nanjing Street No.155, Heping District, Shenyang City 110001, China.
Donghu
D
Zhang
D000818:Animals; D052160:Benzothiazoles / Q000097:blood / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000191:economics / Q000379:methods*; D004791:Enzyme Inhibitors / Q000097:blood* / Q000737:chemistry; D057230:Limit of Detection; D008297:Male; D010080:Oxazoles / Q000097:blood* / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000191:economics / Q000379:methods*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
D052160:Benzothiazoles; D004791:Enzyme Inhibitors; D010080:Oxazoles; C000614239:WSJ-537; D014969:Xanthine Oxidase
LC–MS/MS; Pharmacokinetics; Rats; WSJ-537