Fragmentation Pathway of Synthetic Cannabinoids with an Indole/Indazole-3-Carboxamide Structure Bearing a 1-Carbamoylpropyl Group Using UPLC-Q-TOF MS

A large number of new psychoactive substances (NPS) have gained much distribution and popularity on the global market in the last few years. By December 2016, 106 countries and territories have reported the emergence of a cumulative total of 739 different NPS to United Nations Office on Drugs and Crime (UNODC) Early Warning Advisory (EWA), far exceeding the 251 substances currently controlled under the International Drug Conventions. Indeed, NPS are proliferating at an unprecedented rate and pose a significant risk to public health and a challenge to drug policy. NPS can be categorized in terms of similarity in chemical structure and/or by their major pharmacological effects (for example, synthetic cannabinoids, synthetic cathinones, phenethylamines, tryptamines, and piperazines, etc). Among all the NPS reported to UNODC by the end of 2016, synthetic cannabinoids constitute the largest category in terms of the number of different substances reported. Since the identification of the first synthetic cannabinoid in 2006, more than 230 synthetic cannabinoids have been reported. In 2015-2016, a series of seventeen synthetic cannabinoids with an indole/indazole-3-carboxamide structure bearing a 1-carbamoylpropyl group were identified by ultra performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-Q-TOF MS), gas chromatography-mass spectrometry (GC/MS), and nuclear magnetic resonance spectroscopy (NMR). The compounds have very high cannabimimetic activity which have caused mass severe intoxication and deaths. The mass-spectral fragmentations of these compounds following collision-induced dissociation (CID) were studied. Compounds were analyzed on Acquity UPLC CSH^TM C18 column (100 mm×2.1 mm×1.7 μm) with 0.1% formic acid aqueous solution (A)-acetonitrile (B) as mobile phase for gradient elution. The data were collected using Q-TOF MS at positive electrospray ion mode. The fragmentation behaviors especially the MS fragmentation rules were compared. According to the structure and the typical fragmentations, these compounds were divided into different typical types, and each type has its special fragments that can be easily identified. This work will be helpful to assist forensic laboratories in identifying these kinds of compounds or other substances with similar structure in their case work.