Abstract：
Dried blood spot (DBS) analysis has been an inherent part of sports drug testing through the technological advancements of the past decade. Trimetazidine, a non-threshold banned substance, is excreted into urine after a dose of the permitted drug lomerizine. Therefore, a lomerizine-specific metabolite (M6) is analyzed to confirm the origin of trimetazidine in traditional urine analysis. Application studies were conducted to develop an analytical method for trimetazidine applicable to DBS. These studies comprise (1) the effect of different sampling sites on the detection of trimetazidine, (2) the determination of the appropriate trimetazidine level required for DBS analysis, and (3) differentiating between trimetazidine and lomerizine use. A high-resolution mass spectrometric method for detecting trimetazidine in DBS was validated. After oral administration of trimetazidine (n = 7), venous and capillary blood (fingertip and upper arm) were spotted on cellulose paper. Trimetazidine could be identified in DBS in all subjects up to 60 h after administration. The limit of detection was 0.05 ng/ml, and the limit of identification was 0.06 ng/ml, suggesting the minimum required performance level of 0.2 ng/ml. In the fingertip capillary blood, biases of 9.7% (vs. upper arm) and 13.0% (vs. vein) were observed in the trimetazidine intensity; however, there were no concerns in the qualitative analysis. After administering lomerizine (n = 10), the intact lomerizine has a strong peak intensity in blood compared to trimetazidine. Contrary to urine analysis, the M6 was less detectable in blood. Laboratories should confirm intact lomerizine whenever trimetazidine is identified in DBS.
摘要：
通过过去十年的技术进步，干血斑点（DBS）分析一直是运动药物测试的固有部分。曲美他嗪,非阈值禁用物质，在一定剂量的允许药物洛美利嗪后排泄到尿液中。因此,分析了洛美利嗪特异性代谢物（M6），以确认传统尿液分析中曲美他嗪的来源。进行了应用研究，以开发适用于DBS的曲美他嗪分析方法。这些研究包括（1）不同采样位点对曲美他嗪检测的影响，（2）确定DBS分析所需的适当曲美他嗪水平，和（3）区分曲美他嗪和洛美利嗪的使用。验证了检测DBS中曲美他嗪的高分辨率质谱方法。口服曲美他嗪（n=7）后，静脉和毛细血管血（指尖和上臂）被发现在纤维素纸上。在给药后60小时内，所有受试者的DBS中都可以鉴定出曲美他嗪。检出限为0.05ng/ml，鉴定极限为0.06ng/ml，建议最低要求的性能水平为0.2ng/ml。在指尖毛细血管血液中，9.7%的偏差(与上臂)和13.0%(vs.静脉)在曲美他嗪强度中观察到；然而，定性分析没有问题。服用洛美利嗪（n=10）后，与曲美他嗪相比，完整的洛美利嗪在血液中具有很强的峰值强度。与尿液分析相反，M6在血液中检测较少。每当在DBS中发现曲美他嗪时，实验室应确认完整的洛美利嗪。
