National Reference Laboratory of Veterinary Drug Residues (HZAU), Huazhong Agricultural University, Wuhan 430070, PR China.
Rapid Commun Mass Spectrom. 2010 Apr 15;24(7):909-18. doi: 10.1002/rcm.4460.
Mequindox, 3-methyl-2-quinoxalinacetyl-1,4-dioxide, is a quinoxaline-N,N-dioxide used in veterinary medicine as a antibacterial in China. To gain an understanding of the interspecies differences in the metabolism of mequindox, comparative metabolite profiles were qualitatively and quantitatively carried out for the first time in rat, chicken and pig liver microsomes by high-performance liquid chromatography combined with hybrid ion trap/time-of-flight mass spectrometry. A total of 14 metabolites were characterized based on their accurate MS(2) spectra and known structure of mequindox. The in vitro metabolic pathways of mequindox in three species were proposed as N-->O group reduction, carbonyl reduction, N-->O group reduction followed by carbonyl reduction or methyl mono-hydroxylation. A metabolic pathway involving N-->O group reduction followed by acetyl group mono-hydroxylation in only chicken was also proposed. There was also quantitative species difference for mequindox metabolism in three species. 1-Desoxymequindox was the main metabolite in all species, but otherwise there were some qualitative interspecies differences in mequindox major metabolites. This work has revealed biotransformation characteristics of mequindox among different species, and moreover will further facilitate the explanations of the biological activities of mequindox in animals.
美喹多司，3-甲基-2-喹喔啉乙酰基-1,4-二氧化物，是一种用于兽医的喹喔啉-N,N-二氧化物，在中国被用作抗菌剂。为了了解美喹多司在不同物种间代谢的差异，首次在大鼠、鸡和猪肝微粒体中通过高效液相色谱-混合离子阱/飞行时间质谱联用进行了定性和定量的比较代谢产物分析。基于美喹多司的准确 MS(2)图谱和已知结构，共鉴定了 14 种代谢产物。提出了美喹多司在三种物种中的体外代谢途径为 N-->O 基团还原、羰基还原、N-->O 基团还原后羰基还原或甲基单羟化。还提出了仅在鸡中存在的 N-->O 基团还原后乙酰基单羟化的代谢途径。三种物种中美喹多司代谢也存在定量的种间差异。1-去氧美喹多司是所有物种中的主要代谢产物，但美喹多司主要代谢产物在不同物种间存在一些定性的种间差异。这项工作揭示了美喹多司在不同物种间的生物转化特征，并且将进一步促进对美喹多司在动物体内生物活性的解释。
