title: In vitro metabolism of cyadox in rat, chicken and swine using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry.
abstract: In this work, metabolites of cyadox (CYX) produced by liver microsomes, primary hepatocytes and intestinal microflora systems of rat, chicken and swine were identified and elucidated using ultra-performance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS). Expected and unexpected metabolites were found out using Metabolynx(XS) software by automatically comparing MS(E) data from the sample and control. The metabolites were reliably characterized by accurate MS/MS spectra and their different fragmentation pathways. In total twenty-four metabolites were identified in the three in vitro systems, fifteen of which were novel. The results revealed the main metabolic pathways of CYX were N→O group reduction, hydroxylation and hydrolysis reactions. Besides, methylation and acetylation reactions which represented phase II drug biotransformations were recognized in the in vitro systems of chicken firstly. It also showed that the metabolic capacity and rapidity of chicken and swine was greater than rat, with some differences in metabolic fate and metabolite varieties. This work contributes to the comprehensive understanding of in vitro metabolism of CYX, and will provide an important basis for further in vivo metabolism study and toxicological safety evaluation.
authors.affiliation: College of Veterinary Medicine, China Agricultural University, PR China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Wu
authors.forename: Linxia
authors.initials: L
authors.lastname: Li
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Shen
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Kaili
authors.initials: K
authors.lastname: Liu
authors.forename: Suxia
authors.initials: S
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002645:Chickens; D002853:Chromatography, Liquid / Q000379:methods*; D022781:Hepatocytes / Q000378:metabolism; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000382:microbiology; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D011810:Quinoxalines / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013552:Swine; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D011810:Quinoxalines; C020728:cyadox