title: In vitro and in vivo metabolite profiling of valnemulin using ultraperformance liquid chromatography-quadrupole/time-of-flight hybrid mass spectrometry.
abstract: Valnemulin, a semisynthetic pleuromutilin derivative related to tiamulin, is broadly used to treat bacterial diseases of animals. Despite its widespread use, metabolism in animals has not yet been fully investigated. To better understand valnemulin biotransformation, in this study, metabolites of valnemulinin in in vitro and in vivo rats, chickens, swines, goats, and cows were identified and elucidated using ultraperformance liquid chromatography-quadrupole/time-of-flight hybrid mass spectrometry (UPLC-Q/TOF-MS). As a result, there were totally 7 metabolites of valnemulin identified in vitro and 75, 61, and 74 metabolites detected in in vivo rats, chickens, and swines, respectively, and the majority of metabolites were reported for the first time. The main metabolic pathways of valnemulin were found to be hydroxylation in the mutilin part (the ring system) and the side chain, oxidization on the sulfur of the side chain to form S-oxides, hydrolysis of the amido bond, and acetylization in the amido of the side chain. In addition, hydroxylation in the mutilin part was proposed to be the primary metabolic route. Furthermore, the results revealed that 2β-hydroxyvalnemulin (V1) and 8α-hydroxyvalnemulin (V2) were the major metabolites for rats and swines and S-oxides (V6) in chickens.
authors.affiliation: College of Veterinary Medicine, China Agricultural University, Beijing Laboratory for Food Quality and Safety and Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety , Beijing 100193, People's Republic of China.
authors.forename: Shupeng
authors.initials: S
authors.lastname: Yang
authors.forename: Weimin
authors.initials: W
authors.lastname: Shi
authors.forename: Dingfei
authors.initials: D
authors.lastname: Hu
authors.forename: Suxia
authors.initials: S
authors.lastname: Zhang
authors.forename: Huiyan
authors.initials: H
authors.lastname: Zhang
authors.forename: Zhanhui
authors.initials: Z
authors.lastname: Wang
authors.forename: Linli
authors.initials: L
authors.lastname: Cheng
authors.forename: Feifei
authors.initials: F
authors.lastname: Sun
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Shen
authors.forename: Xingyuan
authors.initials: X
authors.lastname: Cao
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents; D002415:Cats; D002645:Chickens; D002851:Chromatography, High Pressure Liquid; D004224:Diterpenes / Q000032:analysis / Q000378:metabolism / Q000493:pharmacokinetics; D005260:Female; D005506:Food Contamination / Q000032:analysis; D006041:Goats; D006900:Hydroxylation; D008297:Male; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000737:chemistry / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D013552:Swine; D019155:Veterinary Drugs
chemical_list: D000890:Anti-Infective Agents; D004224:Diterpenes; D019155:Veterinary Drugs; C117845:valnemulin
keywords: UPLC-Q/TOF-MS; identification; metabolites; pleuromutilin; valnemulin