Abstract：
The identification of trimetazidine, a medicine used for treating stable angina pectoris and for preventing angina attacks, has been recently observed in doping cases involving high profile athletes from various countries over the world. In all the files where the authors have been involved, the urine concentration of trimetazidine was low (<2 ng/mL), and the athletes argued that contamination was the source of their adverse analytical finding. It is possible to challenge imposed sanctions in relation to an adverse analytical finding, but it is the responsibility of the athlete to demonstrate he/she is innocent and can qualify for no fault or negligence. When the delay between the urine collection and the notification of the violation was not too long (less than 6 months), these athletes requested a head hair test. Trimetazidine was analyzed by an original LC-MS/MS method involving pH 9.5 borate buffer overnight incubation of 20 mg and subsequent solvents extraction in presence of trimetazidine-D8 used as internal standard. Linearity was verified from 1 to 200 pg/mg (R2 = 0.9987). Limit of detection of the method was 0.1 pg/mg. The hair specimen of a male subject, collected 4 weeks after single oral ingestion of 20 mg trimetazidine, tested positive at 146 pg/mg in the corresponding segment. Concentrations of trimetazidine measured in several hair specimens (n = 5) collected from athletes challenging their anti-doping rule violation were below 1 pg/mg, which is consistent with incidental exposure due to contamination. This is the first evidence that trimetazidine is incorporated in human hair after a single therapeutic dose administration.
摘要：
曲美他嗪的鉴定，一种用于治疗稳定型心绞痛和预防心绞痛发作的药物，最近在涉及来自世界各国的知名运动员的兴奋剂案件中观察到。在所有涉及作者的文件中，曲美他嗪的尿液浓度低（<2ng/mL），运动员认为污染是他们不利的分析结果的来源。有可能就不利的分析结论对施加的制裁提出质疑，但运动员有责任证明他/她是无辜的，没有过错或疏忽。当尿液收集和违规通知之间的延迟不太长（少于6个月）时，这些运动员要求进行头发测试。通过原始LC-MS/MS方法分析曲美他嗪,该方法包括pH9.5硼酸盐缓冲液过夜孵育20mg,随后在用作内标的曲美他嗪-D8存在下进行溶剂萃取。从1至200μg/mg(R2=0.9987)证实线性。该方法的检出限为0.1pg/mg。男性受试者的头发样本，单次口服20mg曲美他嗪后4周收集，在相应的部分测试为146pg/mg。从挑战违反反兴奋剂规则的运动员收集的几个头发样本（n=5）中测得的曲美他嗪浓度低于1pg/mg，这与由于污染造成的偶然暴露是一致的。这是曲美他嗪在单次治疗剂量给药后掺入人头发中的第一个证据。
