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

IF 2.6 3区医学 Q2 BIOCHEMICAL RESEARCH METHODS

Drug Testing and Analysis Pub Date : 2024-10-30 DOI:10.1002/dta.3819

Zhongquan Li, Bing Liu, Yirang Wang, Chunyang Yu, Xin Xu, Peijie Chen

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引用次数: 0

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.

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人类肝脏微粒体中伐莫龙的代谢特征：对反兴奋剂的影响

瓦莫洛尔酮是传统糖皮质激素的潜在替代品，因其副作用小、药效学特性优越而在运动医学领域大有可为。本研究旨在调查这种新型合成环糊精类固醇消炎药的代谢特性，阐明其在体外人体肝微粒体（HLMs）中的代谢途径，从而为评估其对运动员的潜在风险提供科学依据。所有化合物均采用液相色谱-高分辨质谱法（LC-HRMS）进行检测，并使用 Compound Discoverer 3.3 软件进行代谢物鉴定。在 HLMs 模型中，成功鉴定出 12 种伐莫罗隆代谢物，包括 10 种 I 期代谢物和 2 种 II 期代谢物。其中，还原代谢物 M1 的峰面积最大，表明它是主要代谢途径之一。脱氢化合物 M2 的峰面积位居第二，进一步阐明了瓦莫罗隆的代谢特征。这项研究系统地鉴定了 HLMs 中伐莫洛龙的代谢物结构，为该药物的药代动力学和生物标志物研究提供了重要数据。这些发现不仅加深了人们对其代谢机制的了解，还为评估其在运动医学中的安全性和有效性提供了科学依据。同时，这些发现有助于更好地规范和控制瓦莫洛龙在竞技体育中的使用，确保比赛的公平性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Drug Testing and Analysis BIOCHEMICAL RESEARCH METHODS-CHEMISTRY, ANALYTICAL

CiteScore

5.90

自引率

24.10%

发文量

191

审稿时长

2.3 months

期刊介绍： As the incidence of drugs escalates in 21st century living, their detection and analysis have become increasingly important. Sport, the workplace, crime investigation, homeland security, the pharmaceutical industry and the environment are just some of the high profile arenas in which analytical testing has provided an important investigative tool for uncovering the presence of extraneous substances. In addition to the usual publishing fare of primary research articles, case reports and letters, Drug Testing and Analysis offers a unique combination of; ‘How to’ material such as ‘Tutorials’ and ‘Reviews’, Speculative pieces (‘Commentaries’ and ‘Perspectives'', providing a broader scientific and social context to the aspects of analytical testing), ‘Annual banned substance reviews’ (delivering a critical evaluation of the methods used in the characterization of established and newly outlawed compounds). Rather than focus on the application of a single technique, Drug Testing and Analysis employs a unique multidisciplinary approach to the field of controversial compound determination. Papers discussing chromatography, mass spectrometry, immunological approaches, 1D/2D gel electrophoresis, to name just a few select methods, are welcomed where their application is related to any of the six key topics listed below.