Identification and analytical characteristics of synthetic cannabinoids with an indazole-3-carboxamide structure bearing a N-1-methoxycarbonylalkyl group

Abstract

Illicit new psychoactive substances (NPS) are a serious threat to health throughout the world. Such NPS do not usually pass preliminary pharmacological trials. In 2014, we identified a series of five new synthetic cannabinoids with an indazole-3-carboxamide structure bearing an N-1-methoxycarbonylalkyl group. The compounds have very high cannabimimetic activity which has caused mass severe intoxication and deaths. The compounds were identified by means of gas chromatography-mass spectrometry (GC-MS), including high-resolution mass spectrometry (GC-HRMS), ultra-high-performance liquid chromatography-high-resolution tandem mass spectrometry (UHPLC-HRMS(2)), and (1)H and (13)C nuclear magnetic resonance spectroscopy (NMR). The peculiarities of mass-spectral fragmentation of the compounds after electron ionization (EI) ionization and collision-induced dissociation (CID) were studied. The analytical characteristics reported for the compounds will enable their identification in a variety of materials seized from criminals.Graphical Abstract.

Identification and analytical characterization of six synthetic cannabinoids NNL‐3, 5F–NPB‐22‐7N, 5F–AKB‐48‐7N, 5F–EDMB‐PINACA, EMB‐FUBINACA, and EG‐018

“…The difference between the protonated molecule of 5 and MMB-FUBINACA (C 21 H 23 FN 3 O 3 + ) [28,29] was an additional CH 2 [28] The 13 C NMR spectrum of 5 was similar to that of MMB-FUBINACA, [28] except for the O-ethyl moiety (positions 1″' to 2″') as shown in Table 6. The difference between the protonated molecule of 5 and MMB-FUBINACA (C 21 H 23 FN 3 O 3 + ) [28,29] was an additional CH 2 [28] The 13 C NMR spectrum of 5 was similar to that of MMB-FUBINACA, [28] except for the O-ethyl moiety (positions 1″' to 2″') as shown in Table 6.…”

Identification of MDMB-FUBINACA in commercially available e-liquid formulations sold for use in electronic cigarettes

“…Regarding the pharmacological effect of this compound, it might be referred as a synthetic cannabinoid (SCB) or cannabimimetic drug. Even though MDMB-FUBINACA is available worldwide via the Internet and the abuse of the drug seems to be increasing [1] there is little to no scientific/medical data concerning the pharmacology, pharmacokinetics, biotransformation or toxicology of the drug. Animal studies of intraperitoneal ( i.p .)…”

“…Hypothermia and bradycardia are typically observed following administration of cannabinoids like tetrahydrocannabinol (THC), as well as, with structurally distinct cannabimimetic indole and indazole derivatives, in rats [3] and mice [4, 5]. Additionally, in vitro binding studies have demonstrated that MDMB-FUBINACA is a potent agonist for the CB1 and CB2 receptors [1, 2]. MDMB-FUBINACA is presently unscheduled by US Drug Enforcement Agency (DEA).…”

Current applications of high-resolution mass spectrometry for the analysis of new psychoactive substances: a critical review

“…Few studies have involved the use of both LC and GC coupled to HRMS. Schevyrin et al [22][23][24] published a series of articles reporting the detection of several SCs for the first time in smoke mixtures from Russia and Belarus using both LC and GC coupled to QTOF-MS. The combination of both chromatography methods was used in lieu of these compounds having spectra in commercial libraries for GC-MS.…”

“…Powders and crystalline solids were largely prepared using solvent extraction or dilution typically with methanol or acetonitrile for MS analyses utilizing LC or GC separation. Schevyrin et al [22][23][24] dissolved smoke mixtures in methanol followed by an additional filtration step with a cellulose membrane. The extraction of blotter papers has been achieved by soaking the paper in methanol for 6 hours [25][26][27].…”