Institute of Biochemistry, Center for Preventive Doping Research, German Sport University Cologne, Cologne, Germany (J.B., A-M. G., A.T., H.G., M.T.); University Hospital Muenster (UKM), Department of Clinical and Surgical Andrology, Centre of Reproductive Medicine and Andrology, Muenster, Germany (S.K., E.N.); Faculty of Medical and Life Sciences, Furtwangen University, Villingen-Schwenningen, Germany (F.W.); Centre for Urology, Neuss, Germany (E.G.); and European Monitoring Center for Emerging Doping Agents (EuMoCEDA), Cologne/Bonn, Germany (H.G., M.T.).
Institute of Biochemistry, Center for Preventive Doping Research, German Sport University Cologne, Cologne, Germany (J.B., A-M. G., A.T., H.G., M.T.); University Hospital Muenster (UKM), Department of Clinical and Surgical Andrology, Centre of Reproductive Medicine and Andrology, Muenster, Germany (S.K., E.N.); Faculty of Medical and Life Sciences, Furtwangen University, Villingen-Schwenningen, Germany (F.W.); Centre for Urology, Neuss, Germany (E.G.); and European Monitoring Center for Emerging Doping Agents (EuMoCEDA), Cologne/Bonn, Germany (H.G., M.T.)
Drug Metab Dispos. 2024 Oct 16;52(11):1313-1322. doi: 10.1124/dmd.124.001845.
Exogenous substances, including drugs and chemicals, can transfer into human seminal fluid and influence male fertility and reproduction. In addition, substances relevant in the context of sports drug testing programs, can be transferred into the urine of a female athlete (after unprotected sexual intercourse) and trigger a so-called adverse analytical finding. Here, the question arises as to whether it is possible to distinguish analytically between intentional doping offenses and unintentional contamination of urine by seminal fluid. To this end, 480 seminal fluids from nonathletes were analyzed to identify concentration ranges and metabolite profiles of therapeutic drugs that are also classified as doping agents. Therefore, a screening procedure was developed using liquid chromatography connected to a triple quadrupole mass spectrometer, and suspect samples (i.e., samples indicating the presence of relevant compounds) were further subjected to liquid chromatography-high-resolution accurate mass (tandem) mass spectrometry. The screening method yielded 90 findings (including aromatase inhibitors, selective estrogen receptor modulators, diuretics, stimulants, glucocorticoids, beta-blockers, antidepressants, and the nonapproved proliferator-activated receptor delta agonist GW1516) in a total of 81 samples, with 91% of these suspected cases being verified by the confirmation method. In addition to the intact drug, phase-I and -II metabolites were also occasionally observed in the seminal fluid. This study demonstrated that various drugs including those categorized as doping agents partition into seminal fluid. Monitoring substances and metabolites may contribute to a better understanding of the distribution and metabolism of exogenous substances in seminal fluid that may be responsible for the impairment of male fertility. SIGNIFICANCE STATEMENT: This study demonstrates that doping agents as well as clinically relevant substances are transferred/eliminated into seminal fluid to a substantial extent and that knowledge about drug levels (and potential consequences for the male fertility and female exposure) is limited. The herein generated new dataset provides new insights into an important and yet little explored area of drug deposition and elimination, and hereby a basis for the assessment of contamination cases by seminal fluid in sports drug testing.
外源性物质，包括药物和化学物质，可转移至人体精液中，并影响男性生育力和生殖功能。此外，在运动药物检测计划中相关的物质可转移至女性运动员的尿液中（无保护性行为后），并引发所谓的阳性分析结果。在此，出现了一个问题，即是否有可能从分析的角度区分故意的兴奋剂违规和精液对尿液的无意污染。为此，分析了 480 份非运动员的精液，以确定也被归类为兴奋剂的治疗性药物的浓度范围和代谢物特征。因此，使用液相色谱连接三重四极杆质谱仪开发了一种筛选程序，对疑似样本（即表明存在相关化合物的样本）进行进一步的液相色谱-高分辨精确质量（串联）质谱分析。该筛选方法在 81 个样本中共发现了 90 个结果（包括芳香酶抑制剂、选择性雌激素受体调节剂、利尿剂、兴奋剂、糖皮质激素、β-受体阻滞剂、抗抑郁药和未经批准的增殖激活受体 δ 激动剂 GW1516），其中 91%的可疑病例通过确证方法得到了验证。除了完整的药物外，在精液中还偶尔观察到 I 期和 II 期代谢物。本研究表明，包括归类为兴奋剂的各种药物都分配到精液中。监测物质和代谢物可能有助于更好地了解外源性物质在精液中的分布和代谢，这可能是导致男性生育力受损的原因。意义：本研究表明，兴奋剂以及具有临床相关性的物质在很大程度上被转移/消除到精液中，并且对药物水平（以及对男性生育力和女性暴露的潜在影响）的了解有限。本研究生成的新数据集为药物沉积和消除的一个重要但研究甚少的领域提供了新的见解，并为运动药物检测中精液污染案例的评估提供了依据。
