Sun Feifei, Yang Shupeng, Zhang Huiyan, Zhou Jinhui, Li Yi, Zhang Jinzhen, Jin Yue, Wang Zhanhui, Li Yanshen, Shen Jianzhong, Zhang Suxia, Cao Xingyuan
College of Veterinary Medicine and Beijing Laboratory for Food Quality and Safety, Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety, National Reference Laboratory of Veterinary Drug Residues, China Agricultural University , Beijing 100193, People's Republic of China.
Bee Research Institute and Bee Product Quality Supervision and Testing Center, Laboratory of Risk Assessment for Quality and Safety of Bee Products, Ministry of Agriculture, Chinese Academy of Agricultural Sciences , Beijing 100093, People's Republic of China.
J Agric Food Chem. 2017 Jan 11;65(1):199-207. doi: 10.1021/acs.jafc.6b04377. Epub 2016 Dec 27.
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, 2β- and 8α-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 8α-hydroxy-tiamulin, N-deethyl-tiamulin, and 8α-hydroxy-N-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 (2β-hydroxy-tiamulin, N-deethyl-tiamulin, and 2β-hydroxy-N-deethyl-tiamulin) of tiamulin in chickens had larger yields, which implied that 2β-hydroxy-mutilin or N-deethyl-tiamulin was more likely to be regarded as the potential marker residue of tiamulin in chickens.
泰妙菌素是一种在兽医实践中广泛用于治疗猪和家禽痢疾及肺炎的抗菌药物。然而，关于泰妙菌素在农场动物体内的代谢情况，人们了解得非常有限。为了更好地理解泰妙菌素的生物转化过程，在本研究中，我们利用超高效液相色谱与四极杆/飞行时间质谱联用技术，对大鼠、鸡、猪、山羊和奶牛体内外的泰妙菌素代谢产物进行了鉴定和阐释。结果表明，共鉴定出26种泰妙菌素的体内外代谢产物，其中大多数代谢产物是首次被发现。在所有农场动物中，泰妙菌素在截短侧耳素部分（环系统）经历I相羟基化代谢途径，侧链发生S-氧化和N-去乙基化反应，未检测到II相代谢产物。其中，2β-和8α-羟基化以及N-去乙基化是泰妙菌素在农场动物体内的主要代谢途径。此外，我们还提出8a-羟基泰妙菌素和8a-羟基-N-去乙基泰妙菌素可被羟基化为8a-羟基截短侧耳素，这是泰妙菌素在猪体内的标记残留物。此外，在不同农场动物中观察到泰妙菌素代谢存在显著的种间差异。猪体内泰妙菌素可能的标记残留物为8α-羟基泰妙菌素、N-去乙基泰妙菌素和8α-羟基-N-去乙基泰妙菌素，这与欧洲药品评估局提出的假设一致。然而，本研究结果表明，鸡体内泰妙菌素的三种代谢产物（2β-羟基泰妙菌素、N-去乙基泰妙菌素和2β-羟基-N-去乙基泰妙菌素）产量较高，这意味着2β-羟基截短侧耳素或N-去乙基泰妙菌素更有可能被视为鸡体内泰妙菌素的潜在标记残留物。
