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A novel xanthine oxidase inhibitor WSJ-557 study on pharmacokinetics and tissue distribution in rats by UPLC–MS/MS

Zhang, Donghu, Yang, Tian, Lin, Jianyang
Journal of chromatography 2019 v.1113 pp. 77-83
bioavailability, drugs, enzyme inhibitors, ethyl acetate, gout, intestines, intravenous injection, liquid-liquid extraction, oral administration, pharmacokinetics, rats, stomach, tandem mass spectrometry, tissue distribution, tissues, ultra-performance liquid chromatography, xanthine oxidase
As a novel non-purine xanthine oxidase inhibitor, WSJ-557 is a potential drug for gout. To determine the WSJ-557 concentration in plasma and various tissues of rats, a fast and sensitive method was first established by the ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) in this paper. The liquid–liquid extraction of ethyl acetate was adopted for the sample preparation, and carbamazepine was taken as the internal standard. In the process of chromatographic separation, MRM transitions for WSJ-557 and carbamazepine (internal standard, IS) were m/z 316.1 → 260.0 and m/z 237.0 → 194.0, correspondingly. The great linearity of WSJ-557 in all bio-samples was found in the corresponding concentration range (r > 0.99). The intra- and inter-day precision (RSD%) were below 9.5% in various tissues and plasma, whose accuracy (RE%) was within ±9.2%. This method was resoundingly employed to the WSJ-557 study on rat pharmacokinetics and tissue distribution after the intravenous administration and oral administration. The average absolute bioavailability (F) of WSJ-557 was 6.48%. The highest distribution level of gastric and intestinal tissues indicated that WSJ-557 was first absorbed in the stomach and intestine. Moreover, this analytical method provides a significant approach for the further development and investigation of WSJ-557.