Comprehensive Analysis of Tiamulin Metabolites in Various Species of Farm Animals Using Ultra-High-Performance Liquid Chromatography Coupled to Quadrupole/Time-of-Flight

文献类型： 外文期刊

第一作者： Sun, Feifei

作者： Sun, Feifei;Zhang, Huiyan;Wang, Zhanhui;Shen, Jianzhong;Zhang, Suxia;Cao, Xingyuan;Sun, Feifei;Zhang, Huiyan;Wang, Zhanhui;Shen, Jianzhong;Zhang, Suxia;Cao, Xingyuan;Yang, Shupeng;Zhou, Jinhui;Li, Yi;Zhang, Jinzhen;Jin, Yue;Yang, Shupeng;Zhou, Jinhui;Li, Yi;Zhang, Jinzhen;Jin, Yue;Li, Yanshen

作者机构：

关键词： tiamulin;comparative metabolism;UHPLC-Q/TOF;liver microsomes;farm animals;in vivo

期刊名称：JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY （ 影响因子：5.279； 五年影响因子：5.269 ）

ISSN：

年卷期：

页码：

收录情况： SCI

摘要： Tiamulin is an antimicrobial widely used in veterinary practice to treat dysentery and pneumonia in pigs and poultry. However, knowledge about the metabolism of tiamulin is very limited in farm animals. To better understand the biotransformation of tiamulin, in the present study, in vitro and in vivo metabolites of tiamulin in rats, chickens, swine, goats, and cows were identified and elucidated using ultra-high performance liquid chromatography coupled to quadrupole/time-of-flight. As a result, a total of 26 metabolites of tiamulin, identified in vitro and in vivo, and majority of metabolites were revealed for the first time. In all farm animals, tiamulin undergoes phase I metabolic routes of hydroxylation in the mutilin part (the ring system), S-oxidation and N-deethylation on side chain, and no phase II metabolite was detected. Among these, 2 beta- and 8 alpha-hydroxylation and N-deethylation were the main metabolic pathways of tiamulin in farm animals. In addition, we have put forward that 8a-hydroxy-tiamulin and 8a-hydroxy-N-deethyl-tiamulin could be hydroxylated into 8a-hydroxy-mutilin, the marker residue of tiamulin in swine. Furthermore, a significant interspecies difference was observed on the metabolism of tiamulin among various farm animals. The possible marker residues for tiamulin in swine were 8a-hydroxy-tiamulin, N-deethyl-tiamulin, and 8 alpha-hydroxyN-deethyl-tiamulin, which were consistent with the hypothesis proposed by the European Agency for the Evaluation of Medicinal Products. However, results in present study indicated that three metabolites (2 beta-hydroxy-tiamulin, N-deethyl-tiamulin, and 2 beta-hydroxy-N-deethyl-tiamulin) of tiamulin in chickens had larger yields, which implied that 2 beta-hydroxy-mutilin or N-deethyltiamulin was more likely to be regarded as the potential marker residue of tiamulin in chickens.

分类号： R15`S

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