College of Veterinary Medicine, National Reference Laboratory of Veterinary Drug Residues (SCAU), South China Agricultural University, Guangzhou 510642, China.
J Chromatogr B Analyt Technol Biomed Life Sci. 2012 Jan 15;881-882:96-106. doi: 10.1016/j.jchromb.2011.12.008. Epub 2011 Dec 15.
Mequindox (MEQ), 3-methyl-2-quinoxalinacetyl-1,4-dioxide, is widely used in Chinese veterinary medicine as an antimicrobial and feed additive. Its toxicities have been reported to be closely related to its metabolism. To understand more clearly the metabolic pathways of MEQ, its metabolism in chickens was studied using liquid chromatography coupled with electrospray ionization hybrid linear trap quadrupole orbitrap (LC-LTQ-Orbitrap) mass spectrometry. The structures of the MEQ metabolites and their product ions were easily and reliably characterized based on the accurate MS-squared spectra and known structure of MEQ. Twenty-four metabolites were detected in chicken plasma, bile, faeces, and tissues, of which 12 were detected in vivo for the first time. The major metabolic pathways reported previously for in vitro metabolism of MEQ in chicken microsomes were confirmed in this study, including N→O group reduction, carbonyl reduction, and methyl mono-hydroxylation. In addition, deacetylation and acetyl-hydroxylation of MEQ were shown to be important metabolic pathways. Collectively, these data contribute to our understanding of the in vivo metabolism of MEQ.
美喹多司（MEQ），即 3-甲基-2-喹喔啉乙酰-1,4-二氧化物，作为一种抗菌药物和饲料添加剂，在中国兽医临床上广泛应用。其毒性与其代谢密切相关。为了更清楚地了解 MEQ 的代谢途径，本研究采用液相色谱-电喷雾电离线性阱轨道阱质谱联用（LC-LTQ-Orbitrap MS）技术，研究了 MEQ 在鸡体内的代谢情况。基于准确的 MS² 谱和 MEQ 的已知结构，很容易且可靠地对 MEQ 代谢物及其产物离子的结构进行了表征。在鸡血浆、胆汁、粪便和组织中检测到 24 种 MEQ 代谢物，其中 12 种为首次在体内检测到。本研究证实了先前报道的 MEQ 在鸡微粒体中体外代谢的主要代谢途径，包括 N→O 基团还原、羰基还原和甲基单羟化。此外，还表明 MEQ 的去乙酰化和乙酰化羟化是重要的代谢途径。这些数据有助于我们了解 MEQ 的体内代谢情况。
