The ADEBAR project: European and international provision of analytical data from structure elucidation and analytical characterization of NPS

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New chemical moieties continue to appear in synthetic cannabimimetics (SC), the largest group of new psychoactive substances in the EU. We describe the first comprehensive characterisation of the novel SC Cumyl‐Tosyl‐Indazole‐3‐Carboxamide (Cumyl‐TsINACA) (N‐[2‐phenylpropan‐2‐yl]‐1‐tosyl‐1H‐indazole‐3‐carboxamide) from seized case samples. Structure elucidation was performed within the EU‐project ADEBAR plus to facilitate confident identification by other researchers and practitioners worldwide. Characteristic MS fragmentations include the cleavage of the sulfonamide bond (S‐N), the aryl sulfone bond (C‐S) and the elimination rearrangement of SO2 in the side chain. Cumyl‐TsINACA is a full receptor agonist at hCB1 (Emax = 228%) with very weak binding affinity (Ki = 292 nm) and low functional activity (EC50 = 31 μm). Thermal degradation of Cumyl‐TsINACA was observed under GC conditions. The degree to which the tosyl side chain is cleaved due to pyrolysis primarily depends on solvent, the use of glass wool in the liner and injector temperature. The determination of the constitution by NMR spectroscopy was ambiguous due to the high number of neighbouring, non‐proton‐bearing atoms. Therefore, other possible structures compatible with the NMR correlations were generated using the WebCocon software. The unambiguous structural evidence was finally obtained by spectra comparison after the synthesis of Cumyl‐TsINACA. The low thermal stability, as well as the low affinity and potency, renders this compound unfavourable for the use as a psychoactive substance. Thus, we do not expect widespread adoption of this SC.

Section: Introductionsupporting

confidence: 64%

supporting

confidence: 58%

Structure elucidation of the novel synthetic cannabinoid Cumyl‐Tosyl‐Indazole‐3‐Carboxamide (Cumyl‐TsINACA) found in illicit products in Germany

Pulver

Schönberger

Weigel

et al. 2022

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“…A sample received on the 29th of September 2021, by the EU‐project ADEBAR plus, also allowed the detection of ADB‐FUBIATA on paper from a seizure of July 2021 by the state police of Schleswig‐Holstein. The chemical identity of ADB‐FUBIATA in this seizure was confirmed by NMR analysis in mid‐October 2021 23,24 …”

Section: Letter Codes For Building Blocks Identified So Farmentioning

confidence: 64%

“…Up until the introduction of the hydrazide linker, all linkers feature the common carbonyl group. October 2021 23,24. ADB-FUBIATA was also detected in powder and e-liquid samples,seized by police in China, following a class-wide ban on SCs in July 2021.…”

mentioning

confidence: 99%

EMCDDA framework and practical guidance for naming synthetic cannabinoids

Pulver¹,

Fischmann²,

Gallegos

et al. 2022

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Synthetic cannabinoids (SCs), often sold as “legal” replacements for cannabis, are the largest group of new psychoactive substances monitored by the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). Currently, close to 240 structurally heterogeneous SCs are monitored through the European Union (EU) Early Warning System, and attributing consistent, informative, and user‐friendly names to SCs has been a challenge in the past. Over time, several naming conventions have been employed with the aim of making SCs more easily recognizable by non‐chemists, including regulators. To achieve this, the names assigned need to contain detailed information on the structural features present in the substance. This work provides a theoretical framework and a practical hands‐on guideline for consistent naming of SCs, which is easy to understand and can be applied by the forensic community, researchers, clinical practitioners, and policy‐makers. The proposed framework builds on the established letter code system for molecular building blocks (core, linker, linked group, and tail) implemented by the EMCDDA in 2013 and has been expanded to incorporate additional structural features through substitution. The scope of the issue of attributing semi‐systematic code names is illustrated, and earlier approaches used for naming SCs are discussed. The concepts and rules of the EMCDDA framework are described through a flowchart that provides a basis for naming new SCs, a graphical overview of the chemical diversity of SCs, and a detailed list of the SCs identified in the EU by the Early Warning System of the EMCDDA for reference.

“…Structure elucidation and analytical characterization were performed within the project ADBEBAR plus 20 utilizing gas chromatography–mass spectrometry (GC–MS), liquid chromatography‐electrospray ionization‐(high resolution‐)mass spectrometry (LC‐ESI‐(HR‐)MS), attenuated total reflection Fourier‐transform infrared spectroscopy (ATR‐FTIR), GC‐solid state infrared spectroscopy (GC‐sIR), Raman spectroscopy, and nuclear magnetic resonance (NMR) analysis. The analytical data were shared with the EMCDDA at the time of identification 21…”

Section: Introductionmentioning

confidence: 99%

A new synthetic cathinone: 3,4‐EtPV or 3,4‐Pr‐PipVP? An unsuccessful attempt to circumvent the German legislation on new psychoactive substances

Pulver

Riedel

Westphal³

et al. 2022

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Synthetic cathinones comprise psychostimulants with desired effects like euphoria, increased vigilance, appetite suppression, and—mainly depending on certain structural features—entactogenic properties. 3,4‐EtPV (1‐(bicyclo[4.2.0]octa‐1,3,5‐trien‐3‐yl)‐2‐(pyrrolidin‐1‐yl)pentan‐1‐one) was first mentioned in an online drug forum in September 2021, where its imminent synthesis was announced. The goal was to produce a legal alternative to the phenylethylamines already banned by the German NpSG. In February and June 2022, two samples labeled with the name and molecular structure of 3,4‐EtPV were analyzed. The molecular structure of the obviously mislabeled compound was elucidated and comprehensively characterized within the ADEBAR project. The synthetic cathinone identified differed from the declared 3,4‐EtPV by a 3,4‐propylene bridge instead of a 3,4‐ethylene bridge and a piperidine ring instead of a pyrrolidine ring. The short name 3,4‐Pr‐PipVP (3,4‐propylene‐2‐(1‐piperidinyl)valerophenone) was suggested as a semisystematic name in collaboration with the European Monitoring Centre for Drugs and Drug Addiction. Herein, the results of the analyses are discussed and will enable forensic laboratories to update their databases quickly and identify 3,4‐Pr‐PipVP confidently. 3,4‐Pr‐PipVP is already scheduled under the German NpSG. This study highlights that there are ongoing efforts to deliberately circumvent generic definitions given, for example, in the German NpSG and that (unintentional?) mislabeling can be an issue. The end user purchasing substances online can never be sure that the material actually supplied will be the one ordered, and he might receive an illicit drug instead of an uncontrolled one. Furthermore, the purity is always unknown, creating health risks due to unexpected effects and potencies.