Leveraging mass spectrometry fragmentation patterns for accelerated screening and structural elucidation of new...

Etomidate analogues are structural modifiers of etomidate, which also have psychoactive effects, and abuse of them is gradually intensifying. Due to the existence of multiple modification sites in the structures of etomidate, the rate of derivatization is extremely rapid, which brings more difficulties for rapid analysis and accurate identification of these substances in forensic laboratories. Thus, establishing a non-targeted screening and structural identification method can effectively solve this problem. In this study, the structural evolution rules of etomidate analogues were investigated, mainly by modifying the "linking group" and "tail" to obtain new substances. Moreover, the application of the mass fragmentation patterns of etomidate analogues to the rapid screening and structural confirmation of such substances was elaborated in detail. The proposed structures of eight etomidate analogues in the suspicious samples were deduced by GC-QTOF/MS and LC-Q-Orbitrap MS/MS. In ESI-MS/MS mode, the basic ions e (m/z 113) and f (m/z 95) originating from the core of etomidate analogues could be utilized for the non - targeted recognition of these substance. The characteristic fragment ions a and b in EI-MS mode were applicable for identifying the "linker group" and "linker". Meanwhile, the diagnostic ions d, e and f in ESI-MS/MS mode could serve to identify the "core" and "tail". Among the eight etomidate analogues, the structures of compounds 1-4 were further verified via reference substances, and the structures of compounds 5-8 (butomidate, sec-butomidate, 4F-etomidate and CF₃-etomidate) were novel etomidate analogues, which were further confirmed by NMR. This study could provide a good basis for the inference and identification of etomidate analogues.