Mass spectrometric studies on selective androgen receptor modulators (SARMs) using electron ionization and electrospray ionization/collision-induced dissociation
Mass spectrometric studies on selective androgen receptor modulators (SARMs) using electron ionization and electrospray ionization/collision-induced dissociation
复制标题
使用电子电离和电喷雾电离/碰撞诱导解离对选择性雄激素受体调节剂 (SARM) 进行质谱研究
DOI：
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发表时间：
2018
影响因子：
1.3
通讯作者：
D. Volmer
中科院分区：
文献类型：
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作者：
M. Thevis;D. Volmer
选择性雄激素受体调节剂(SARM)已被确定为一类很有前途的候选药物，可能适用于通常与肌肉质量显着减少相关的各种病理情况。由于在精英和业余运动中被怀疑并同时被反复证明滥用SARM，保持不断更新的兴奋剂控制分析方法对于运动药物检测实验室至关重要。这些测试方法主要利用基于质谱学的仪器，因此，对新化合物及其代谢产物的质谱学行为的研究对于全面控制兴奋剂至关重要。本文讨论了三种新的SARM候选药物GSK2881078、PF-06260414和TfM-4AS-1在电子电离和电喷雾电离/碰撞诱导解离下的解离模式。通过使用四极轨道质谱仪的高分辨率/高精度串联质谱仪，获得了关于前体-产物离子关系和元素组成的信息，并随后被用来建议目标化合物的解离路线。这些信息有助于今后关于代谢物结构分配的研究，并加速识别相关物质，如果在体育界分布和/或非法使用的话。
Selective androgen receptor modulators (SARMs) have been identified as a promising class of drug candidates potentially applicable to diverse pathological conditions commonly associated with significantly reduced muscle mass. Due to a suspected and meanwhile repeatedly proven misuse of SARMs in elite and amateur sport, sustaining constantly updated doping control analytical methods is critical for sports drug testing laboratories. These test methods predominantly utilize mass spectrometry-based instrumentations and, consequently, studies on the mass spectrometric behavior of new compounds and, where available, their metabolic products are vital for comprehensive doping controls. In this communication, the dissociation patterns of three new SARM drug candidates referred to as GSK2881078, PF-06260414, and TFM-4 AS-1 as observed under electron ionization as well as electrospray ionization/collision-induced dissociation are discussed. By means of high resolution/high accuracy tandem mass spectrometry employing quadrupole-orbitrap mass analyzers, information on precursor-product ion relationships and elemental compositions was obtained and subsequently utilized to suggest dissociation routes of the target compounds. This information can contribute to future studies concerning structure assignments of metabolites and accelerate the identification of related substances if distributed and/or illicitly used in the world of sport.