Metabolic Characterization of Vamorolone in Human Liver Microsomes: Implications for Anti‐Doping

Abstract

Vamorolone, a potential alternative to conventional glucocorticoids, shows significant promise in sports medicine due to its reduced side effects and superior pharmacodynamic properties. This study aims to investigate the metabolic characteristics of this novel synthetic cyclodextrin‐steroid anti‐inflammatory drug and elucidate the metabolic pathways in human liver microsomes (HLMs) in vitro, thereby providing a scientific basis for assessing its potential risks for athletes. All compounds are detected by liquid chromatography‐high resolution mass spectrometry (LC‐HRMS) and metabolite identification was performed using Compound Discoverer 3.3 software. In the HLMs model, 12 metabolites of vamorolone are successfully identified, including 10 phase I metabolites and 2 phase II metabolites. Among these, the reduction metabolite M1 exhibited the highest peak area, indicating it as one of the primary metabolic pathways. The dehydrogenated compound M2 had the second highest peak area, further elucidating the metabolic characteristics of vamorolone. This study systematically identifies the metabolite structures of vamorolone in HLMs and provide crucial data for the pharmacokinetics and biomarker research of this drug. The findings not only enhance the understanding of its metabolic mechanisms but also offer a scientific basis for evaluating its safety and efficacy in sports medicine. Meanwhile, these discoveries can contribute to better regulation and control of Vamorolone's use in competitive sports, ensuring fairness in competitions.