German Sport University Cologne, Center for Preventive Doping Research/Institute of Biochemistry, Am Sportpark Muengersdorf 6, 50933 Cologne, Germany; European Monitoring Center for Emerging Doping Agents (EuMoCEDA), Cologne/Bonn, Germany.
German Sport University Cologne, Center for Preventive Doping Research/Institute of Biochemistry, Am Sportpark Muengersdorf 6, 50933 Cologne, Germany.
Mol Cell Endocrinol. 2018 Mar 15;464:34-45. doi: 10.1016/j.mce.2017.01.040. Epub 2017 Jan 27.
The class of selective androgen receptor modulators (SARMs) has been the subject of intense and dedicated clinical research over the past two decades. Potential therapeutic applications of SARMs are manifold and focus particularly on the treatment of conditions manifesting in muscle loss such as general sarcopenia, cancer-associated cachexia, muscular dystrophy, etc. Consequently, based on the substantial muscle- and bone-anabolic properties of SARMs, these agents constitute substances with significant potential for misuse in sport and have therefore been added to the Word Anti-Doping Agency's (WADA's) Prohibited List in 2008. Since then, numerous adverse analytical findings have been reported for various different SARMs, which has underlined the importance of proactive and preventive anti-doping measures concerning emerging drugs such as these anabolic agents, which have evidently been misused in sport despite the fact that none of these SARMs has yet received full clinical approval. In this review, analytical data on SARMs generated in the context of research conducted for sports drug testing purposes are summarized and state-of-the-art test methods aiming at intact drugs as well as diagnostic urinary metabolites are discussed. Doping control analytical approaches predominantly rely on chromatography hyphenated to mass spectrometry, which have allowed for appropriately covering the considerable variety of pharmacophores present in SARMs such as the non-steroidal representatives ACP-105, BMS-564929, GLPG0492 (DT-200), LG-121071, LGD-2226, LGD-4033/VK 5211, ostarine/enobosarm, RAD-140, S-40503, etc. as well as steroidal compounds such as MK-0773 and YK-11.
过去二十年,选择性雄激素受体调节剂(SARMs)一直是密集且专注的临床研究的主题。SARMs 的潜在治疗应用多种多样,特别侧重于治疗肌肉减少症等疾病,如一般性肌肉减少症、癌症相关恶病质、肌肉营养不良症等。因此,基于 SARMs 的实质性肌肉和骨骼合成代谢特性,这些药物构成了在体育运动中被滥用的重大潜在物质,因此已在 2008 年被世界反兴奋剂机构(WADA)的禁用清单所收录。自那时以来,已经报道了许多不同 SARMs 的不良分析结果,这突显了针对这些合成代谢剂等新兴药物采取积极和预防性反兴奋剂措施的重要性,尽管这些 SARMs 中没有一种已经获得全面的临床批准,但它们显然已经在体育运动中被滥用。在这篇综述中,总结了为运动药物检测目的进行的研究中生成的 SARMs 的分析数据,并讨论了针对完整药物以及诊断性尿液代谢物的最新测试方法。兴奋剂控制分析方法主要依赖于与质谱联用的色谱技术,这使得能够适当地涵盖 SARMs 中存在的大量不同药效团,如非甾体代表物 ACP-105、BMS-564929、GLPG0492(DT-200)、LG-121071、LGD-2226、LGD-4033/VK 5211、ostarine/enobosarm、RAD-140、S-40503 等,以及甾体化合物,如 MK-0773 和 YK-11。