Structural Confirmation of Synthetic Cannabinoids in Seized Electronic Cigarette Oil: A Combined Mass Spectrometric and Computational Study

Rationale

Synthetic cannabinoid is one of the most used and abused new psychoactive substances, because it can produce a stronger intense pleasure than natural cannabis. Most of newly synthetic cannabinoids are structurally similar to existing synthetic cannabinoids and can be obtained by modifying partial structures of the latters without changing their effects, therefore, the derivatization rules and common fragmentation patterns of synthetic cannabinoids could be used for rapid screening and structural identification of them.

Methods

The derivatization rules of synthetic cannabinoid were summarized, and the common fragmentation pattern of synthetic cannabinoid including three typical cleavage pathways was explored and extended in this work based on combined mass spectrometry and DFT studies. Five synthetic cannabinoids in electronic cigarette oil from a drug case were separated and characterized by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography coupled to high resolution quadrupole Orbitrap mass spectrometry (LC-Q-Orbitrap/MS).

Results

The structures of five synthetic cannabinoids in seized electronic cigarette oil were deduced from EI-MS and high resolution ESI-MSⁿ data, along with the derivatization rules and common fragmentation pattern of synthetic cannabinoids. The proposed structures of these synthetic cannabinoids were further verified by reference substances. Computational study showed that selective cleavage of these compounds was mainly controlled by spin population in EI-MS, but tunneling effect arose from proton transfer in ESI-MSⁿ detection, which was rarely reported in previous works.

Conclusions

Our results showed that EI-MS was suitable for identifying synthetic cannabinoids with aromatic ketone structure, which could also be extended to adamantane linked group. Nevertheless, synthetic cannabinoids with carbamoyl linked group were better characterized by high resolution ESI-MSⁿ compared to EI-MS. This study demonstrated a method with promising potential for rapid and reliable screening of synthetic cannabinoids in mixtures with enhanced detection throughput and operation simplicity.