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J Chromatogr B Analyt Technol Biomed Life Sci. 2019 Apr 15;1113:77-83. doi: 10.1016/j.jchromb.2019.03.013. Epub 2019 Mar 15.

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

Author information

1
Department of Pharmacy, the First Hospital of China Medical University, 155 Nanjing North Street, Shenyang 110001, Liaoning, China; School of Pharmaceutical Science, China Medical University, 77 Puhe Road, Shenyang 110122, Liaoning, China.
2
Department of Pharmacy, the First Hospital of China Medical University, 155 Nanjing North Street, Shenyang 110001, Liaoning, China; School of Pharmaceutical Science, China Medical University, 77 Puhe Road, Shenyang 110122, Liaoning, China. Electronic address: linjianyangydyy@126.com.

Abstract

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.

KEYWORDS:

Bioavailability; Pharmacokinetics; Rats; Tissue distribution; UPLC-MS/MS; WSJ-557

PMID:
30901732
DOI:
10.1016/j.jchromb.2019.03.013
[Indexed for MEDLINE]

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