Synthetic cannabinoid receptor agonists (SCRAs) are psychoactive substances that were first developed for medical research. However, they now account for a large proportion of novel psychoactive substances (NPS), and, since 2008, have been monitored by the European Monitoring Centre for Drug and Drug Addiction (EMCDDA)1.
SCRAs are structurally very diverse. They have a complex molecular structure of four pharmacophore components, which can be modified in a range of ways. It is this which makes them attractive to illicit drug-makers seeking to create novel substances.
The German government first enacted a law (called the NpSG) to control NPS in November 2016. Initially, it set out chemical structures defined by four structural elements: a core structure, which is connected to a linked group by a linker with a defined position, and a side chain attached to a designated nitrogen atom of the core structure. However, when drug-makers started to make new variations to get around the law, the NpSG was amended (July 2019) to include several core structures and substitution patterns2.
At that time, the NpSG covered all the major SCRAs on the drug market. However, drug-makers are constantly finding ways to modify chemical structures so they fall outside the law’s jurisdiction.
In an attempt to keep track of new variations of SCRAs, Germany runs a project co-funded with the EU called Adebar Plus3, which provides structural analysis of new unidentifiable drugs for police and customs forensic laboratories, as well as international groups. All analytical data are published rapidly to share with national and international organizations4. Substances that are identified for the first time in Germany or the EU are immediately reported to the Early Warning System of the EMCDDA.
In November 2019, Adebar Plus produced a comprehensive set of analytical data on a new substance, which they called Cumyl-CBMICA (Cumyl-CycloButylMethyl-IndoleCarboxAmide), and reported it to the EMCDDA. First discovered in Germany in 2019, it was found the next summer in the Netherlands5. Although Germany has updated the NpSG to include the new substance, it is not yet regulated in most European countries.
This study examined Cumyl-CBMICA in the form of herbal material seized by the Bavarian State Police in August 2019, as well as 14 herbal blends bought on-line6. The researchers used a range of techniques to produce a comprehensive description of the substance. These included gas chromatography-mass spectrometry (GC-MS). The proposed molecular formulas of the unknown substance and its most relevant fragments, as suggested by the GC-MS results18, were then confirmed using Liquid Chromatography quadrupole Time-of-Flight mass spectrometry (LC-qToF-MS).
QToF-MS provides both high sensitivity and specificity and is particularly well-suited for investigating newly emerging psychoactive agents. The coupling of Q-TOF-MS with techniques such as liquid or gas chromatography can provide rapid and comprehensive screening solutions. The team used Bruker’s impact II qToF instrument coupled with a Bruker Elute HPLC system. Chromatographic separation was performed on a Bruker Intensity solo 1.8 C18-2 2.1 x 100 mm and a VanGuard BEH C18 1.7 µm guard-column.
The investigation went on to use attenuated total reflection-infrared spectroscopy (ATR-IR), gas chromatography solid-state infrared spectroscopy (GC-sIR), Raman spectroscopy at 785 nm and at 1064 nm, and nuclear magnetic resonance spectrometry (NMR), to provide a detailed structure of the herbal blend.
Bruker offers the most comprehensive solution portfolio for forensic analysis. This includes identification and quantification of narcotics and doping agents, chemical warfare agents, characterization of explosives, detection of food fraud, art and document forgery, environmental forensics including waste analysis and crime scene investigations like glass, fiber and gunshot residue analysis. Bruker’s technologies are applied in day-to-day routine analysis as well as to develop and enhance new methods like in the present study. Our mission of enabling law enforcement to generate coherent and robust data for legal proceedings will make societies safer.
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