Identification and quantification of 10 indole/indazole carboxamide synthetic cannabinoids in 36 herbal blends by gas chromatography‐mass spectrometry and nuclear magnetic resonance spectroscopy

Abstract

Herbal blends containing synthetic cannabinoids have become popular alternatives to marijuana. The number of synthetic cannabinoids and speed of their emergence enable this group of compounds particularly challenging in terms of detection, monitoring, and responding. In this work, both gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance spectroscopy (NMR) methods were developed for the identification and quantification of synthetic cannabinoids in herbal blends. Ten types of indole/indazole carboxamide synthetic cannabinoids, which showed different types of substitutions connected to nitrogen of the indole/indazole carboxamide, were detected in 36 herbal blends. The GC-MS fragmentation routes of indole/indazole carboxamide synthetic cannabinoids were discussed in detail for structure identification purpose. The concentration range of synthetic cannabinoid in 36 herbal blends was 1.9-50.6 mg/g using GC-MS method, while 1.5-49.0 mg/g by NMR method. Nicotine in herbal blends was quantified by NMR method without using reference material, and showed a variation of 5.3-44.7 mg/g. For quantitative analysis, NMR method showed great advantage in the absence of reference material, while GC-MS method showed great merit for multiple-compound analysis when reference material was available. Therefore, for the quantitative analysis of new emerged synthetic cannabinoid in herbal blends, different methods could be chosen by considering whether reference material is available, as well as the number and types of synthetic cannabinoids detected in a single sample.

Identification of AD‐18, 5F‐MDA‐19, and pentyl MDA‐19 in seized materials after the class‐wide ban of synthetic cannabinoids in China

“…In July 2021, China imposed a class‐wide ban on synthetic cannabinoids, with the definition of synthetic cannabinoids by seven core structures (Figures 1a and S1). Before July 2021, indole/indazole carboxamide synthetic cannabinoids were the most prevalent types in China 8 . But after July 2021, some new synthetic cannabinoids that were not covered by the generic definitions have appeared on the recreational drug market.…”

“…Synthetic cannabinoid use has repeatedly been reported to produce serious adverse health effects, including dependence, cardiovascular disease, mental confusion, high blood pressure, acute kidney injury, cancer, and even death 5,6 . Currently, two main types of products containing synthetic cannabinoids are sold on the drug market: herbal blends and e‐liquids 3,7–9 . The number of synthetic cannabinoids, their chemical diversity, and rate of their emergence pose significant challenges in terms of detection, monitoring, and responding.…”

“…Before July 2021, indole/indazole carboxamide synthetic cannabinoids were the most prevalent types in China. 8 But after July 2021, some new synthetic cannabinoids that were not covered by the generic definitions have appeared on the recreational drug market.…”

Identification and analytical characterization of N‐propyl norbutylone, N‐butyl norbutylone, N‐benzyl norheptedrone, and N‐pyrrolidinyl‐3,4‐DMA

“…Quantitative NMR (qNMR) has been widely used for the quantification of NPS. 18,19 Based on the fact that the integral of each signal is proportional to the number of nuclei responsible for that individual resonance for all chemical species in the sample, qNMR provides a linear response without requiring the use of the standard addition method or a calibration curve. 20 In this study, qNMR was applied for the quantification of seized samples.…”

Identification of three novel new psychoactive substances 4F‐AB‐BUTINACA, AB‐PHETINACA, and 2F‐NENDCK

“…With the increase in synthetic cannabinoid substances, the potential for abuse and their toxicity has presented challenges to human health 8 . Synthetic cannabinoid substances have become a major class of illicit drugs in China as well as in European countries in recent years 7–14 . 5F‐AB‐PINACA has been included in China's illicit drug catalogue (edition 2015).…”