Comprehensive profiling of synthetic cannabinoids fragment ions using UPLC-HRMS in conjunction with online databases

This study utilizes Ultra-Performance Liquid Chromatography-High-Resolution Mass Spectrometry (UPLC-HRMS) and integrates open-access online MS databases (e.g., mzCloud) along with analytical software (e.g., Mass Frontier, ChemDraw). By leveraging a well-established structural classification framework, we systematically analyzed the high-resolution mass spectrometry (HRMS) fragmentation pathway and key m/z of known synthetic cannabinoids (SCs). Based on the four common components of synthetic cannabinoids (core, linked group, side chain, and linker), integrate the structural information of known SCs, and obtain HRMS for representative SCs through LC-HRMS analysis. The elemental compositions and chemical properties of recurring or structurally related m/z were individually analyzed with the aid of open-access MS databases and supporting software. The study revealed that the core structures of SCs (such as indole, indazole, and carbazole) produce stable m/z (e.g., m/z 116.050, 144.044) during fragmentation. Additionally, substituents (such as phenyl rings, pyridine rings, and halogenated naphthalenes) and sidechains (such as aliphatic chains and benzyl structures) also generate stable m/z during fragmentation. Moreover, the study uncovered the relationship between the sidechain structures of SCs and neutral losses. The findings could provide significant theoretical and technical support for the metabolic analysis, non-targeted detection, structural identification, and other aspects of drug control research on SCs, and also fill the gap in the comprehensive HRMS characterization of SCs in existing studies.