Quantification of osilodrostat in horse urine using LC/ESI-HRMS to establish an elimination profile for doping control.

IF 1.9 4区医学 Q3 BIOCHEMICAL RESEARCH METHODS Bioanalysis Pub Date : 2024-09-05 DOI:10.1080/17576180.2024.2385848

Hideaki Ishii, Ryo Shigematsu, Shunsuke Takemoto, Yuhiro Ishikawa, Fumiaki Mizobe, Motoi Nomura, Daisuke Arima, Hirokazu Kunii, Reiko Yuasa, Takashi Yamanaka, Sohei Tanabe, Shun-Ichi Nagata, Masayuki Yamada, Gary Ngai-Wa Leung

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Abstract

Aim: The use of osilodrostat, developed as a medication for Cushing's disease but categorized as an anabolic agent, is banned in horses by both the International Federation of Horseracing Authorities and the Fédération Equestre Internationale. For doping control purposes, elimination profiles of hydrolyzed osilodrostat in horse urine were established and the detectability of free forms of osilodrostat and its major metabolite, mono-hydroxylated osilodrostat (M1c), was investigated.Materials & methods: Post-administration urine samples obtained from a gelding and three mares were analyzed to establish the elimination profiles of osilodrostat using a validated method involving efficient enzymatic hydrolysis followed by LC/ESI-HRMS analysis.Results: Applying the validated quantification method with an LLOQ of 0.05 ng/ml, hydrolyzed osilodrostat could be quantified in post-administration urine samples from 48 to 72 h post-administration; by contrast, both hydrolyzed osilodrostat and M1c were detected up to 2 weeks. In addition, confirmatory analysis identified the presence of hydrolyzed osilodrostat for up to 72 h post-administration.Conclusion: For doping control purposes, we recommend monitoring both hydrolyzed M1c and osilodrostat because of the greater detectability of M1c and the availability of a reference material of osilodrostat, which is essential for confirmatory analysis.

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利用 LC/ESI-HRMS 对马尿液中的奥司洛司他（osilodrostat）进行定量，以建立兴奋剂控制的消除曲线。

目的：奥西洛前列素是作为治疗库欣氏症的药物开发的，但被归类为同化制剂，国际赛马联合会和国际马术联合会都禁止在马匹体内使用奥西洛前列素。出于兴奋剂控制目的，我们建立了水解奥司洛前列素在马尿中的消除曲线，并研究了游离形式的奥司洛前列素及其主要代谢物单羟化奥司洛前列素（M1c）的可检测性：对一匹公马和三匹母马用药后的尿液样本进行分析，以确定奥司洛前列素的消除曲线，采用的有效方法包括高效酶水解，然后进行 LC/ESI-HRMS 分析：应用有效的定量方法（LLOQ为0.05 ng/ml），可在用药后48至72小时的尿样中定量检测水解奥司洛前列素；相比之下，水解奥司洛前列素和M1c的检测时间长达2周。此外，确证分析还发现在用药后 72 小时内都存在水解奥司洛前列素：结论：出于兴奋剂控制目的，我们建议同时监测水解 M1c 和奥西前列素，因为 M1c 的可检测性更高，而且可以获得奥西前列素的参照物，这对确证分析至关重要。

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

Bioanalysis BIOCHEMICAL RESEARCH METHODS-CHEMISTRY, ANALYTICAL

CiteScore

3.30

自引率

16.70%

发文量

审稿时长

2 months

期刊介绍： Reliable data obtained from selective, sensitive and reproducible analysis of xenobiotics and biotics in biological samples is a fundamental and crucial part of every successful drug development program. The same principles can also apply to many other areas of research such as forensic science, toxicology and sports doping testing. The bioanalytical field incorporates sophisticated techniques linking sample preparation and advanced separations with MS and NMR detection systems, automation and robotics. Standards set by regulatory bodies regarding method development and validation increasingly define the boundaries between speed and quality. Bioanalysis is a progressive discipline for which the future holds many exciting opportunities to further reduce sample volumes, analysis cost and environmental impact, as well as to improve sensitivity, specificity, accuracy, efficiency, assay throughput, data quality, data handling and processing. The journal Bioanalysis focuses on the techniques and methods used for the detection or quantitative study of analytes in human or animal biological samples. Bioanalysis encourages the submission of articles describing forward-looking applications, including biosensors, microfluidics, miniaturized analytical devices, and new hyphenated and multi-dimensional techniques. Bioanalysis delivers essential information in concise, at-a-glance article formats. Key advances in the field are reported and analyzed by international experts, providing an authoritative but accessible forum for the modern bioanalyst.