Thevis Mario, Kohler Maxie, Thomas Andreas, Maurer Joachim, Schlörer Nils, Kamber Matthias, Schänzer Wilhelm
Center for Preventive Doping Research, Institute of Biochemistry, German Sport University Cologne, Carl-Diem-Weg 6, 50933, Cologne, Germany.
Anal Bioanal Chem. 2008 May;391(1):251-61. doi: 10.1007/s00216-008-1882-6. Epub 2008 Feb 13.
Selective androgen receptor modulators (SARMs) represent a novel class of drugs with tissue-specific agonistic and antagonistic properties, which are prohibited in sports from January 2008 according to the World Anti-Doping Agency. Preventive approaches to restrict the use of SARMs include early implementation of target analytes into doping control screening assays. Five model SARMs were synthesized, four of which are analogs to prostate-specific androgen receptor antagonists with a 5,6-dichloro-benzimidazole nucleus. The fifth SARM is a muscle-tissue specific agonist with a bicyclic hydantoin structure (BMS-564929). Dissociation pathways after negative electrospray ionization were studied using an LTQ-Orbitrap mass analyzer, and diagnostic product ions and common fragmentation patterns were employed to establish a screening procedure that target the intact SARMs as well as putative metabolic products. Sample preparation based on solid-phase extraction and subsequent LC-MS/MS measurement allowed for detection limits of 1-20 ng/mL, intra- and interday precisions of between 2.4 and 13.2% and between 6.5 and 24.2%, respectively. Recoveries varied from 89 to 106%, and tests for ion suppression or enhancement effects were negative for all analytes. [figure: see text]
选择性雄激素受体调节剂（SARMs）是一类具有组织特异性激动和拮抗特性的新型药物，根据世界反兴奋剂机构规定，自2008年1月起在体育赛事中被禁用。限制使用SARMs的预防措施包括在兴奋剂检测筛查分析中尽早采用目标分析物。合成了五种模型SARMs，其中四种是具有5,6-二氯苯并咪唑核的前列腺特异性雄激素受体拮抗剂类似物。第五种SARM是具有双环乙内酰脲结构的肌肉组织特异性激动剂（BMS-564929）。使用LTQ-Orbitrap质谱分析仪研究了负电喷雾电离后的解离途径，并采用诊断产物离子和常见的碎裂模式建立了针对完整SARMs及其假定代谢产物的筛查程序。基于固相萃取的样品制备及随后的LC-MS/MS测量，检测限为1 - 20 ng/mL，日内和日间精密度分别在2.4%至13.2%和6.5%至24.2%之间。回收率在89%至106%之间，所有分析物的离子抑制或增强效应测试均为阴性。[图：见正文]
