National Reference Laboratory of Veterinary Drug Residues (HZAU), Huazhong Agricultural University, Wuhan, Hubei 430070, P.R. China.
Rapid Commun Mass Spectrom. 2011 Jan 30;25(2):341-8. doi: 10.1002/rcm.4833.
Carbadox (methyl-3-(2-quinoxalinylmethylene)-carbazate-N(1),N(4)-dioxide) is a chemotherapeutic growth promoter added to feed for starter pigs. In this work, the metabolism of carbadox in rat, pig and chicken liver microsomes has been studied firstly. The incubation mixtures were then processed and analyzed for metabolites with a sensitive and reliable method based on high-performance liquid chromatography combined with hybrid ion trap/time-of-flight mass spectrometry (LC/MS-IT-TOF). With the help of chromatographic behavior and accurate mass measurements, it is possible to rapidly and reliably characterize the metabolites of carbadox. The structural elucidations of these metabolites were performed by comparing the changes in the accurate molecular masses and fragment ions generated from precursor ions with those of parent drug. The present results showed that the metabolism of carbadox in liver microsomes had qualitative species-difference. A total of seven metabolites were identified in rat liver microsomes. Five metabolites (Cb1-Cb3, Cb5, Cb7) were observed in pig and chicken liver microsomes. In addition, metabolite Cb6 was also detected in chicken liver microsomes. The peak areas of the metabolites in the three species are different. For the formations of Cb1, Cb2, Cb5 and Cb6, the rank order was rat>chicken>pig; Cb3; pig~chicken>rat. Cb1, Cb2 and Cb3 have been previously reported, whereas the other four metabolites were novel. The N→O group reduction and hydroxylation followed by N→O group reduction were the main metabolic pathways for carbadox in the three species.
卡巴氧（3-（2-喹喔啉基亚甲基）-氨基脲-N（1），N（4）-二氧化物）是一种添加到仔猪饲料中的化学治疗生长促进剂。在这项工作中，首先研究了卡巴氧在大鼠、猪和鸡肝微粒体中的代谢。然后，使用基于高效液相色谱与混合离子阱/飞行时间质谱（LC/MS-IT-TOF）的灵敏可靠方法对孵育混合物进行处理和分析以检测代谢产物。借助色谱行为和精确质量测量，可以快速可靠地鉴定卡巴氧的代谢产物。通过比较前体离子产生的精确分子质量和碎片离子的变化，对这些代谢产物的结构进行了阐明。与母体药物相比。本研究结果表明，肝微粒体中卡巴氧的代谢具有定性的种属差异。在大鼠肝微粒体中鉴定出了 7 种代谢产物。在猪和鸡肝微粒体中观察到 5 种代谢产物（Cb1-Cb3、Cb5、Cb7）。此外，在鸡肝微粒体中还检测到代谢产物 Cb6。三种物种的代谢产物峰面积不同。对于 Cb1、Cb2、Cb5 和 Cb6 的形成，顺序为大鼠>鸡>猪；Cb3；猪~鸡>大鼠。Cb1、Cb2 和 Cb3 以前曾有报道，而其他四种代谢物是新的。在三种物种中，N→O 基团还原和随后的 N→O 基团还原以及羟化是卡巴氧的主要代谢途径。
