FG-4592 is a hypoxia-inducible factor inhibitor that has been approved for therapeutic use in some countries. This class of compounds can increase the oxygen carrying capacity of the blood and thus have the potential to be used as performance enhancing agents in sports. The purpose of this study was to investigate the detection of FG-4592 and metabolites in equine plasma and mane hair following a multiple dose oral administration to two Thoroughbred racehorses, to identify the best analytical targets for doping control laboratories. Urine samples were also analysed, and the results compared to previously published urine data. Liquid chromatography-high resolution mass spectrometry was used for metabolite identification in urine and plasma. Liquid chromatography–tandem mass spectrometry was used for full sample analysis of urine, plasma and hair samples and generation of urine and plasma profiles. FG-4592 and a mono-hydroxylated metabolite were detected in plasma. FG-4592 was detected with the greatest abundance and gave the longest duration of detection, up to 312 h post-administration, and would be the recommended target in routine doping samples. FG-4592 was detected in all mane hair samples collected post-administration, up to 166 days following the final dose, showing extended detection can be achieved with this matrix. To the best of the authors' knowledge, this is the first report of FG-4592 and metabolites in equine plasma and hair samples. Urine results were consistent with the previously published data, with FG-4592 offering the best target for detection and longest detection periods.

中文翻译：

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口服给药后马血浆、尿液和毛发中 FG-4592 及其代谢物的检测

FG-4592 是一种缺氧诱导因子抑制剂，已在一些国家批准用于治疗用途。这类化合物可以增加血液的携氧能力，因此有可能用作运动中的表现增强剂。本研究的目的是调查两匹纯种赛马多次口服给药后马血浆和鬃毛中 FG-4592 及其代谢物的检测情况，以确定兴奋剂控制实验室的最佳分析目标。还分析了尿液样本，并将结果与​​之前发布的尿液数据进行比较。采用液相色谱-高分辨率质谱法鉴定尿液和血浆中的代谢物。使用液相色谱-串联质谱法对尿液、血浆和头发样本进行全样本分析，并生成尿液和血浆谱。在血浆中检测到 FG-4592 和单羟基化代谢物。FG-4592 的丰度最高，检测持续时间最长，给药后长达 312 小时，将成为常规兴奋剂样本中的推荐目标。在最终剂量后最多 166 天收集的所有鬃毛样本中均检测到 FG-4592，这表明使用该基质可以实现延长检测。据作者所知，这是马血浆和毛发样本中 FG-4592 及其代谢物的首次报告。尿液结果与之前公布的数据一致，FG-4592提供了最佳的检测靶点和最长的检测周期。