Equine Forensic Unit, Central Veterinary Research Laboratory, Dubai, United Arab Emirates.
Drug Test Anal. 2021 Jun;13(6):1203-1215. doi: 10.1002/dta.3014. Epub 2021 Feb 23.
Hypoxia-inducible factor (HIF) stabilizer belongs to a novel class of pharmacologically active substances, which are capable of inducing the endogenous erythropoietic system. The transcriptional activator HIF has been shown to significantly increase blood hemoglobin and is well set for the treatment of anemia resulting from chronic kidney disease. This research work reports a comprehensive study of the most popular HIF stabilizer roxadustat and its metabolites in thoroughbred horse urine after oral administration. The plausible structures of the detected metabolites were postulated using liquid chromatography-high-resolution mass spectrometry. Under the experimental condition 13 metabolites (7 phase I, 1 phase II, and 5 conjugates of phase I metabolism) were positively detected (M1-M13). The major phase I metabolites identified were formed by hydroxylation. Dealkylated and hydrolyzed phase I metabolites were also observed in this study. In phase II, a glucuronic acid conjugate of roxadustat was detected as the major metabolite. The sulfonic acid conjugates were observed to be formed from phase I metabolites. The characterized in vivo metabolites can potentially serve as target analytes for doping control analysis; hence, the result is an important tool for assessing its use and abuse in competitive sport.
缺氧诱导因子（HIF）稳定剂属于一类新型的具有药理活性的物质，能够诱导内源性红细胞生成系统。转录激活因子 HIF 已被证明能显著增加血液血红蛋白，非常适合治疗慢性肾病引起的贫血。本研究全面研究了口服罗沙司他及其代谢物在纯种马尿液中的情况。使用液质联用技术推测了所检测到的代谢物的可能结构。在实验条件下，共检测到 13 种代谢物（7 种 I 相代谢物、1 种 II 相代谢物和 5 种 I 相代谢物的结合物）（M1-M13）。鉴定的主要 I 相代谢物是通过羟化形成的。本研究还观察到脱烷基和水解的 I 相代谢物。在 II 相中，检测到罗沙司他的葡萄糖醛酸缀合物为主要代谢物。观察到磺酸缀合物是由 I 相代谢物形成的。所鉴定的体内代谢物可能作为兴奋剂控制分析的靶标分析物；因此，该结果是评估其在竞技体育中使用和滥用的重要工具。
