In vitro metabolic profiles of motolimod by using liquid chromatography tandem mass spectrometry: metabolic stability, metabolite characterization and species comparison

Publication date: Available online 7 February 2019Source: Journal of Pharmaceutical and Biomedical AnalysisAuthor(s): Zeyun Li, Songfeng Zhao, Yongliang Yuan, Lizhen Zhang, Zhizhen Song, Xin Tian, Xiaojian ZhangAbstractMotolimod (VTX-2337) is an agonist of toll-like receptor 8 (TLR8) with potential immune-stimulating and antineoplastic activities. The purpose of this study was to investigate the in vitro metabolic profiles of VTX-2337. The average in vitro T1/2 values were 6.93, 8.71, 7.39, 2.85, and 10.58 min in the liver microsomes of mouse, rat, dog, monkey and human respectively, suggesting that VTX-2337 suffered from extensive metabolism. The metabolites were further profiled and identified by using ultra-high performance liquid chromatography coupled with diode array detector and Q-Exactive-Orbitrap tandem mass spectrometer (UHPLC-DAD-Q-Exactive-Orbitrap-MS) operated in positive ion mode. A total of 20 metabolites were detected and their identities were characterized based on their accurate masses, fragment ions and retention times. M13 (depropylation) was the most abundant metabolite in all species. M14 (oxygenation) was also the major metabolite in the liver microsomes of mouse, rat, monkey and human. M1, M5, M10, M15, and M16 were specifically detected in mouse, while M6 and M17 were monkey-specific. All the metabolites present in human could be found in animal species. The metabolic pathways of VTX-2337 referred to oxygenation, hydrolysis, depropylation, and dehyd...
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research