甲在体外代谢物识别用于记录在兴奋剂中暴露的甲
Alessandro Di Giorgi1, Gloria Daziani1, Anastasio Tini1
1Unit of Forensic Toxicology, Section of Legal Medicine, Department of Biomedical Sciences and Public Health-Marche Polytechnic University, Ancona, Italy.
Journal of analytical toxicology
|July 16, 2025
概括
这项研究确定了人类肝细胞中特定的甲代谢物. 这些新型标记物可以改善体育兴奋剂控制中滥用利尿剂的检测.
科学领域:
- 药理学和毒理学 药理学和毒理学
- 反兴奋剂科学反兴奋剂科学
- 代谢学 代谢学 代谢学
背景情况:
- 世界反兴奋剂机构 (WADA) 禁止在S5类别下使用利尿剂,因为它们在体育运动中具有掩蔽和减肥作用.
- 作为一种类似于 thiazide 的利尿剂的 Chlorthalidone 是医疗处方的,但也被滥用用于兴奋剂目的.
- 精确检测chlorthalidone及其代谢物对于反兴奋剂执法至关重要.
研究的目的:
- 为了研究人类中甲的新陈代谢.
- 为了确定运动员中甲消费的特定代谢物标志物.
- 为反兴奋剂查建立可靠的分析目标.
主要方法:
- 使用GLORYx软件在中预测甲的代谢物.
- 在体外化甲与汇集的人类肝细胞以模拟肝脏新陈代谢.
- 使用液体染色学高分辨率并列质谱法 (LC-HRMS/MS) 分析化物.
- 软件辅助数据挖掘用于代谢物识别.
主要成果:
- 在分析预测了11种II期代谢物,其中N-乙化是最可能的转化.
- 在人类肝细胞化器中发现了两种新的chlorthalidone代谢物.
- 这些已识别的代谢物显示了利米丁部分的减少或基化.
结论:
- 已识别的代谢物是特定于chlorthalidone的.
- 这些新型代谢物在反兴奋剂检测中作为甲检测的潜在标.
- 这项研究提高了用于检测体育运动中滥用利尿剂的分析能力.
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