Structural Development and Mass Spectrometry Analysis of Synthetic Cannabinoids

The abuse of new psychoactive substances has spread around the world. Synthetic cannabinoids (SCs) is an important group. Since the first discovery of JWH-018 in Europe in 2008, SCs have multiplied rapidly and become the focus of drug control worldwide. Statistics from the Drug Intelligence and Forensic Center of the Ministry of Public Security of China showed that the proportion of SCs in suspected drug samples seized had increased from 18-5% to 72% in 2017-2019. To this, our country drug control administration department makes positive response. A series of new anti-drug policies had been introduced since 2015. Fifty-three SCs were legally controlled until the end of 2018. China had issued total ban on SCs since July 1st, 2021. However, because of the great structural variability of SCs, it is of great significance to identify the key target structures and summarize the characteristics of the common spectrum of similar drugs in judicial practice. In this paper, 27 synthetic cannabinoids were selected, including the new synthetic cannabinoids with high prevalence in recent years and potential drug structures that had not been reported but were inferred based on the structural evolution trend of synthetic cannabinoids. The method of gas chromatography-mass spectrometry (GC-MS) was used to collect data of the selected SCs under electron ionization mode (EI). The results indicated that the SCs were mainly composed of core, linker, linked group and sidechain. Among them, the core of new SCs gradually changed from formyl indole to indole/indazolamide, which would produce characteristic fragments of m/z 144, 145, respectively. The fragmentation of the linker part mainly occurred on both sides of the carbonyl group. The tertiary carbon atoms, methyl butyrate and butylamide from the linked groups led to diversified fragmentation easily. Neutral loss frequently happened in the part of sidechain, which resulted in the formation of characteristic fragments such as fluoro-butyl (m/z 74), fluoro-pentyl (m/z 88) and pentenyl (m/z 68). The 7 SCs prepared according to the predicted structure shared similar fragmentation pathways with the 22 SCs abused both domestically and abroad. The variation of SCs based on the structures defined in law would gradually decrease and the structural stability would be enhanced after the total ban of SCs was issued. The mass fragmentation pathway mentioned above can provide technical support for the species identification of new SCs, as well as the prevention of drug variation. © 2022 Chinese Society for Mass Spectrometry. All rights reserved.