uhplc - q - Orbitrap质谱法测定尿和体外微体培养样品中盐酸克仑特罗代谢物的生物合成和鉴定:人与牛代谢的比较

IF 2.7 3区 医学 Q2 BIOCHEMICAL RESEARCH METHODS
Anuar Gómez-Tagle, Claudia Bressan, Rosa Ventura, Alan Álvarez-Sanchez, Enrique Cardenas-Yong, Benjamín Velasco-Bejarano
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引用次数: 0

摘要

克伦特罗(Clb)是一种β2激动剂药物,被世界反兴奋剂机构(WADA-AMA)列入比赛期间和比赛外禁止使用的物质清单。世界反兴奋剂机构认可的实验室已经检测到一些不利的分析结果,但运动员经常声称结果是由于饮食污染。本文采用液相色谱-电喷雾q - extive - orbitrap质谱分析和比较了牛微粒体孵育和牛和人尿中Clb代谢产物的排泄,以确定Clb代谢的差异。尿液样品在正离子和负离子模式下进行电喷雾分析之前进行固相萃取处理。采用包合物离子表触发平行监测反应(PRM)进行质谱/质谱实验。代谢物鉴定的策略包括使用来自母体药物的诊断片段离子,根据准确的质量变化寻找典型的生物转化。这种方法成功鉴定了8种代谢物,包括一种新的n -甲基化形式的Clb,这是首次在这里报道。此外,在牛尿液中发现的四种代谢物为进一步研究区分非故意兴奋剂提供了巨大的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Biosynthesis and Identification of Clenbuterol Metabolites in Urine and In Vitro Microsome Incubation Samples Using UHPLC-Q-Exactive Orbitrap Mass Spectrometry: A Comparison Between Human and Bovine Metabolism.

Clenbuterol (Clb) is a β2-agonist drug included in the list of substances prohibited during and out of competition by the World Anti-Doping Agency (WADA-AMA). Several adverse analytical findings have been detected by accredited WADA laboratories, but athletes often claim that results are due to dietary contamination. In this contribution, bovine microsomal incubation and the excretion of bovine and human urinary metabolites of Clb were analyzed and compared using liquid chromatography electrospray Q-Exactive-Orbitrap mass spectrometry to determine differences in Clb metabolism. Urine samples were processed by solid-phase extraction prior to electrospray analysis in both the positive and negative ion modes. MS/MS experiments were obtained by parallel monitoring reaction (PRM) triggered by an inclusion ions list. The strategy for metabolite identification involved the search for typical biotransformation based on accurate mass shifts using diagnostic fragment ions from the parent drug. This approach successfully identified eight metabolites, including a novel N-methylated form of Clb, reported here for the first time. Additionally, four metabolites found exclusively in bovine urine offer significant potential for further research aimed at distinguishing unintentional doping.

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来源期刊
Drug Testing and Analysis
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.
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