Thevis Mario, Kohler Maxie, 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.
Rapid Commun Mass Spectrom. 2007;21(21):3477-86. doi: 10.1002/rcm.3247.
Selective androgen receptor modulators (SARMs) represent a class of emerging drugs with high potential for misuse in sports, and therefore members of this group are banned as anabolic agents by the World Anti-Doping Agency. Preventive approaches to restrict their use include early implementation of target analytes into doping control screening assays and evaluation of the mass spectrometric behavior of these drugs to allow their unequivocal identification as well as the characterization of structurally related compounds and metabolic products. Four model SARMs with the 6-alkylamino-2-quinolinone structure, including the advanced drug candidate LGD-2226, were synthesized. Fragmentation pathways after positive electrospray ionization and collision-induced dissociation were studied using an LTQ Orbitrap mass analyzer, and diagnostic product ions and common dissociation pathways were employed to establish a screening procedure targeting intact quinolinone-based SARMs as well as putative metabolic products such as dealkylated analogues. Therefore, features of a triple quadrupole mass analyzer such as multiple reaction monitoring and precursor ion scanning were utilized. Sample preparation based on commonly employed liquid-liquid extraction and subsequent liquid chromatographic/tandem mass spectrometric measurement allowed for detection limits of 0.01-0.2 ng/mL, and intra- and interday precisions between 3.2 and 8.5% and between 6.3 and 16.6%, respectively. Recoveries varied from 81 to 98%, and tests for ion suppression or enhancement effects were negative for all analytes.
选择性雄激素受体调节剂（SARMs）是一类新出现的药物，在体育界有被滥用的高风险，因此该类药物被世界反兴奋剂机构列为禁用的合成代谢剂。限制其使用的预防措施包括尽早将目标分析物纳入兴奋剂检测筛查分析方法，并评估这些药物的质谱行为，以便能明确鉴定它们以及对结构相关化合物和代谢产物进行表征。合成了四种具有6-烷基氨基-2-喹啉酮结构的模型SARMs，包括先进的候选药物LGD-2226。使用LTQ Orbitrap质谱分析仪研究了正电喷雾电离和碰撞诱导解离后的碎裂途径，并利用诊断性产物离子和常见的解离途径建立了一种筛查程序，以检测完整的基于喹啉酮的SARMs以及推定的代谢产物，如脱烷基类似物。因此，利用了三重四极杆质谱分析仪的一些特性，如多反应监测和前体离子扫描。基于常用液-液萃取的样品制备以及随后的液相色谱/串联质谱测量，检测限为0.01 - 0.2 ng/mL，日内和日间精密度分别在3.2%至8.5%和6.3%至16.6%之间。回收率在81%至98%之间，所有分析物的离子抑制或增强效应测试均为阴性。
