关键词: Alternative matrix Anabolic steroids Anti-doping Diuretics Sports drug testing World Anti-Doping Agency

Mesh : Animals Humans Anabolic Agents Canrenone / analysis Doping in Sports / methods Diuretics / analysis Feces / chemistry Hair / chemistry Substance Abuse Detection / methods

来  源:   DOI:10.1007/s00204-023-03667-1   PDF(Pubmed)

Abstract:
Hair analysis is a crucial method in forensic toxicology with potential applications in revealing doping histories in sports. Despite its widespread use, knowledge about detectable substances in hair is limited. This study systematically assessed the detectability of prohibited substances in sports using a multifaceted approach. Initially, an animal model received a subset of 17 model drugs to compare dose dependencies and detection windows across different matrices. Subsequently, hair incorporation data from the animal experiment were extrapolated to all substances on the World Anti-Doping Agency\'s List through in-silico prediction. The detectability of substances in hair was further validated in a proof-of-concept human study involving the consumption of diuretics and masking agents. Semi-quantitative analysis of substances in specimens was performed using ultra-performance liquid chromatography-tandem mass spectrometry. Results showed plasma had optimal dose dependencies with limited detection windows, while urine, faeces, and hair exhibited a reasonable relationship with the administered dose. Notably, hair displayed the highest detection probability (14 out of 17) for compounds, including anabolic agents, hormones, and diuretics, with beta-2 agonists undetected. Diuretics such as furosemide, canrenone, and hydrochlorothiazide showed the highest hair incorporation. Authentic human hair confirmed diuretic detectability, and their use duration was determined via segmental analysis. Noteworthy is the first-time reporting of canrenone in human hair. Anabolic agents were expected in hair, whereas undetectable compounds, such as peptide hormones and beta-2 agonists, were likely due to large molecular mass or high polarity. This study enhances understanding of hair analysis in doping investigations, providing insights into substance detectability.
摘要:
头发分析是法医毒理学中的重要方法,在揭示体育运动中的兴奋剂史方面具有潜在的应用价值。尽管它广泛使用,关于头发中可检测物质的知识是有限的。这项研究使用多方面的方法系统地评估了运动中违禁物质的可检测性。最初,动物模型接受了17种模型药物的子集,以比较不同基质的剂量依赖性和检测窗口.随后,通过计算机预测,将动物实验的毛发掺入数据外推到世界反兴奋剂机构清单上的所有物质。在涉及利尿剂和掩蔽剂消耗的概念验证人体研究中,进一步验证了头发中物质的可检测性。使用超高效液相色谱-串联质谱法对标本中的物质进行半定量分析。结果显示血浆具有最佳剂量依赖性,检测窗口有限,而尿液,粪便,和头发表现出与给药剂量的合理关系。值得注意的是,头发显示出最高的化合物检测概率(17个中的14个),包括合成代谢药物,荷尔蒙,和利尿剂,与β-2激动剂未被发现。利尿剂如呋塞米,Canrenone,和氢氯噻嗪显示最高的头发掺入。正宗的人类头发证实了利尿剂的可检测性,并通过分段分析确定其使用持续时间。值得注意的是首次报道人类头发中的canrenone。合成代谢药物预计在头发中,而不可检测的化合物,如肽激素和β-2激动剂,可能是由于分子量大或极性高。这项研究增强了对兴奋剂调查中头发分析的理解,提供对物质可检测性的见解。
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