Center for Preventive Doping Research - Institute of Biochemistry, German Sport University Cologne, Am Sportpark Müngersdorf 6, 50933 Cologne, Germany.
Drug Test Anal. 2009 Aug;1(8):387-92. doi: 10.1002/dta.91.
Non-steroidal and tissue-selective anabolic agents such as selective androgen receptor modulators (SARMs) represent a promising class of therapeutics for the treatment of various diseases such as sarcopenia or cancer cachexia. Advanced compounds of SARMs are based on an arylpropionamide-derived structure and leading drug candidates have successfully completed phase-II-clinical trials. Although none of these therapeutics have been approved, their performance-enhancing qualities and the black-market availability of these products makes them a viable target for misuse in the athletic community. In 2008, SARMs were added to the Prohibited List established by the World Anti-Doping Agency (WADA). That SARMs are the subject of misuse even without clinical approval was proved for the first time by the detection of the drug candidate Andarine (also referred to as S-4, S-3-(4-acetylamino-phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamide), advertised, sold and supplied via the Internet. The oily liquids, declared as green tea extracts and face moisturizer, were assayed using state-of-the-art analytical procedures and S-4 was found at concentrations of approximately 150 mg/mL. The authenticity of the product was demonstrated in comparison to reference material by liquid chromatography, high resolution/high accuracy (tandem) mass spectrometry using positive and negative electrospray ionization, and comparison to reference material. Moreover, an impurity resulting from poor product purification was detected, accounting for approximately 10% of S-4. This consisted of 2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-3-(4-nitro-3-trifluoromethyl-phenylamino)-propionamide. The ease of purchasing non-approved drug candidates that could potentially increase athletic performance demonstrates the need to operate proactively in the continued fight against doping. The early inclusion of emerging drugs into routine sports drug testing procedures is a key element of preventive doping research, limiting the options for cheating athletes who aim to undermine the doping control system.
非甾体类和组织选择性合成代谢药物，如选择性雄激素受体调节剂 (SARMs)，代表了一类有前途的治疗药物，可用于治疗各种疾病，如肌肉减少症或癌症恶病质。SARMs 的先进化合物基于芳基丙酰胺衍生结构，领先的候选药物已成功完成 II 期临床试验。尽管这些治疗方法都没有获得批准，但它们具有增强性能的特点，以及这些产品在黑市上的可获得性，使它们成为运动界滥用的可行目标。2008 年，SARMs 被世界反兴奋剂机构 (WADA) 建立的禁用清单所收录。即使没有临床批准，SARMs 也被首次证明是被滥用的，当时检测到了候选药物 Andarine（也称为 S-4、S-3-（4-乙酰氨基苯氧基）-2-羟基-2-甲基-N-（4-硝基-3-三氟甲基-苯基）-丙酰胺），它是通过互联网宣传、销售和供应的。这些声称是绿茶提取物和面部保湿霜的油性液体，使用最先进的分析程序进行了检测，结果发现 S-4 的浓度约为 150mg/mL。通过液相色谱、正负电喷雾电离的高分辨率/高精度（串联）质谱以及与参比物质的比较，证明了该产品的真实性。此外，还检测到了由于产品纯化不良而产生的杂质，约占 S-4 的 10%。它由 2-羟基-2-甲基-N-（4-硝基-3-三氟甲基-苯基）-3-（4-硝基-3-三氟甲基-苯基氨基）-丙酰胺组成。购买非批准药物候选物的便利性可能会提高运动成绩，这表明需要积极主动地继续打击兴奋剂。将新兴药物尽早纳入常规运动药物检测程序是预防兴奋剂研究的一个关键要素，限制了那些试图破坏兴奋剂控制系统的作弊运动员的选择。
