Equine metabolic investigation of the phosphodiesterase-4 inhibitor ibudilast as a potential performance enhancer

IF 1.8 3区化学 Q4 BIOCHEMICAL RESEARCH METHODS Rapid Communications in Mass Spectrometry Pub Date : 2024-09-22 DOI:10.1002/rcm.9916

Moses Philip, Abdul Khader Karakka Kal, Michael Benedict Subhahar, Tajudheen K. Karatt, Fatma Mohammed Graiban, Meleparappil Muhammed Ajeebsanu, Marina Joseph, Shantymol V. Jose

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Abstract

Rationale

Phosphodiesterase 4 (PDE4) inhibitors are a newer class of drugs that induce bronchodilation and have anti-inflammatory effects, making them susceptible to misuse as performance enhancers in competitive sports.

Methods

This study explores the metabolic conversion of PDE4 inhibitor ibudilast in thoroughbred horses after oral administration and in vitro using equine liver microsomes and Cunninghamella elegans. A liquid chromatography-high resolution mass spectrometry method was used to postulate the plausible structures of the detected metabolites.

Results

A total of 20 in vivo metabolites were identified under experimental conditions, including 12 Phase I and 8 Phase II conjugated metabolites. Phase I metabolites were predominantly formed through hydroxylation (mono-, di-, and tri-hydroxylation). Demethylated metabolites were also identified during this investigation. Additionally, the research detected Phase II metabolites conjugated with glucuronic and sulfonic acids.

Conclusions

The data presented here can assist in detecting the PDE4 inhibitor ibudilast and uncover its illicit use in competitive sports.

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将磷酸二酯酶-4抑制剂伊布司特作为一种潜在的运动表现提升剂的马匹代谢研究。

理由：磷酸二酯酶4（PDE4）抑制剂是一类较新的药物，可诱导支气管扩张并具有抗炎作用，因此在竞技体育中容易被误用为提高成绩的药物：本研究利用马肝脏微粒体和昆明马杆菌，探讨了纯血马口服 PDE4 抑制剂依布司特后在体外的代谢转化。采用液相色谱-高分辨质谱法推测检测到的代谢物的合理结构：结果：在实验条件下，共鉴定出 20 种体内代谢物，包括 12 种第一阶段代谢物和 8 种第二阶段共轭代谢物。第一阶段代谢物主要是通过羟基化（一羟基化、二羟基化和三羟基化）形成的。调查中还发现了脱甲基代谢物。此外，研究还发现了与葡萄糖醛酸和磺酸共轭的第二阶段代谢物：本文提供的数据有助于检测 PDE4 抑制剂依布地司特，并揭露其在竞技体育中的非法使用。

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

Rapid Communications in Mass Spectrometry 化学-分析化学

CiteScore

4.10

自引率

5.00%

发文量

219

审稿时长

2.6 months

期刊介绍： Rapid Communications in Mass Spectrometry is a journal whose aim is the rapid publication of original research results and ideas on all aspects of the science of gas-phase ions; it covers all the associated scientific disciplines. There is no formal limit on paper length ("rapid" is not synonymous with "brief"), but papers should be of a length that is commensurate with the importance and complexity of the results being reported. Contributions may be theoretical or practical in nature; they may deal with methods, techniques and applications, or with the interpretation of results; they may cover any area in science that depends directly on measurements made upon gaseous ions or that is associated with such measurements.