Identification of the novel synthetic cannabinoid-type new psychoactive substance, CH-PIACA, in seized material

Abstract

Synthetic cannabinoids (SCs) remain the largest class of new psychoactive substances (NPS) according to the European Monitoring Centre for Drugs and Drug Addiction (EMDCDDA) and while the number of new analogues that are reported for the first time each year declines, SCs are reported the most compared to other NPS classes. This decline can be seen as a result of legislative changes by different jurisdictions which have sometimes transitioned to a more generalized approach when controlling substances by defining common structural scaffolds rather than explicit structures. While the consequences of such legislative changes have been expected over the years, the introduction of so called “class-wide” bans has put further pressure on clandestine laboratories to synthesize compounds which are out of the scope of the legislation and thus these compounds are initially harder to detect and/or identify in forensic chemistry or medico-legal contexts in the absence of analytical data. Recently, a synthetic cannabinoid with an indole-3-acetamide core-linker scaffold, AD-18 (i.e. ADB-FUBIATA or ADB-FUBIACA), was reported for the first time in China in 2021. Here, an additional cannabinoid with the indole-3-acetamide scaffold, N-cyclohexyl-2-(1-pentyl-1H-indol-3-yl)acetamide (tentatively CH-PIACA) was structurally characterized using gas chromatography – mass spectrometry (GC-MS), liquid chromatography – high-resolution mass spectrometry (LC-HRMS) and nuclear magnetic resonance (NMR) spectroscopy. A beige powder in a zip-lock bag was seized by The Danish Customs Agency and subsampled by combining three aliquots of approximately 1 g after homogenization with a mortar and pestle. Sample solutions for GC-MS and UHPLC-QTOF-MS were prepared by dissolving the material in methanol and 25% methanol + 1% formic acid, respectively. For NMR, 3 mg of the powder was dissolved in DMSO-d6 and filtered into an NMR tube. Routine GC-MS analysis of the seized material yielded a single major peak at 22.156 min with a molecular ion at m/z 326.3 and fragment ions at m/z 200, 144 and 130 in the electron ionization mass spectrum (EI-MS). In addition, a major component was observed at 11.91 min in the UHPLC-QTOF-MS screening which had a precursor ion at m/z 327.2450 corresponding to a compound with a molecular formula of C21H30N2O. Similar product ions were observed in the electrospray ionization tandem MS (ESI-MS/MS) spectrum with m/z 245.1644, 200.1441, 144.0808, 130.0651, 100.1120 and 83.0853. NMR spectroscopy with 1H, 13 C, COSY, HMBC and HSQC indicated that the structure was likely to be a substituted indole with a pentyl chain and N-cyclohexylacetamide at the 1- and 3 positions. This structure was corroborated by the EI-MS and ESI-MS/MS data with the neutral loss of N-cyclohexyl-carboxamide (C7H13NO, 127.0997 Da) via cleavage of the bond between the α and β carbons forming m/z 200.1441, while the product ion at m/z 245.1644 corresponded to the loss of cyclohexene from the amide nitrogen. The loss of the N-cyclohexyl-carboxamide was also followed by the loss of the pentyl chain from the nitrogen of the indole ring to yield m/z 130.0651, while m/z 100.1120 corresponded to the cyclohexylammonium cation. The product ion at m/z 144.0808 was proposed to be due to the loss of both the N-cyclohexyl-carboxamide and cleavage of the pentyl chain to liberate 1-butene. A new SC with the indole-3-acetamide scaffold was identified in a seized material in Denmark and characterized using GC-MS, UHPLC-QTOF-MS and NMR spectroscopy. This marks the second SC with this scaffold that has been reported with further analogues anticipated to emerge in the near future.