ORIGINAL RESEARCH article
Front. Vet. Sci.
Sec. Veterinary Pharmacology and Toxicology
Volume 12 - 2025 | doi: 10.3389/fvets.2025.1660872
Comprehensive in Vivo and in Vitro Metabolic Profiling of Amphenmulin: A Novel Pleuromutilin Derivative Characterized by UHPLC-Q-TOF-MS/MS
Provisionally accepted
- 1South China Agricultural University, Guangzhou, China
- 2Shandong Qilu King-Phar Pharmaceutical Co Ltd, Jinan, China
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Amphenmulin is a novel pleuromutilin derivative with proven excellent antibacterial activity. To investigate its metabolism in animals, ultra-high-performance liquid chromatography coupled with quadrupole/time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS) was employed to analyze and identify in vivo metabolites in rats and chickens and in vitro using human, rat, pig, chicken and beagle dog liver microsomes. We identified 18 metabolites from liver microsomes and 24 and 17 in vivo metabolites for rats and chickens, respectively. The primary amphenmulin metabolic pathways involved sulfur oxidation of the side chain, hydroxylations on the aniline moiety and the parent mutilin nucleus, and the primary in vivo metabolites in rats and chickens were amphenmulinsulfoxide (M2) and hydroxy-amphenmulin (M1). These findings provide a structural basis for further investigation intovaluable evidence for the future in-depth understanding of the pharmacokinetics and safety profile of amphenmulin and serve as a reference for the development and optimization of other pleuromutilin derivatives.
Keywords: Pleuromutilin, UHPLC-Q/TOF, Metabolites, Liver microsomes, in vivo
Received: 07 Jul 2025; Accepted: 08 Aug 2025.
Copyright: © 2025 Wang, Wang, Deng, Su, Tang and Ding. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Huanzhong Ding, South China Agricultural University, Guangzhou, China
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