Identification and quantification of synthetic cannabinoids in ‘spice‐like’ herbal mixtures: A snapshot of the German situation in the autumn of 2012

Abstract

Synthetic compounds mimicking cannabis-like effects are a recent trend. Currently, these so-called synthetic cannabinoids are the largest and fastest growing class of newly appearing designer drugs. Many national authorities are continuously adapting their regulations to keep pace with the permanently changing variety of compounds. We have analyzed eight herbal smoking blends containing synthetic cannabinoids. Altogether, nine compounds could be identified, namely AM-2201, AM-2201-pMe (MAM-2201), AM-1220, AM-1220-azepane, UR-144, XLR-11, JWH-122-pentenyl, AM-2232, and STS-135. Newly appearing compounds were isolated by column chromatography and their structures elucidated by 1D- and 2D-nuclear magnetic resonance (NMR) experiments. In addition, the compounds were investigated by electron ionization-mass spectrometry (EI-MS) and electrospray ionization-tandem mass spectrometry (ESI-MS/MS) to complete the physicochemical dataset. Based on the purified compounds a universal gas chromatography-mass spectrometry (GC-MS) method was developed for the identification and quantification of these compounds in commercial smoking blends. By applying this method, up to five different compounds could be found in such products showing total concentrations from 72 to 303 mg/g smoking blend while individual compounds ranged from 0.4 to 303 mg/g. (1)H NMR spectra of the chiral compounds AM-1220 and its azepane-isomer recorded in the presence of 1 equivalent of (R)-(+)-α-methoxy-α-trifluoromethylphenylacetic acid (MTPA, Mosher's acid) showed them to be racemic mixtures.

Identification and quantification of synthetic cannabinoids in “spice-like” herbal mixtures: update of the German situation for the spring of 2015

“…In accordance with our previous papers [2,13], the atom numbering used is as follows: (a) 2, 3, … for the indole/ indazole moiety, (b) 2 0 , 3 0 , … for the naphthalene moiety or other groups connected to 3-CO-/3-CONH-/3-COO-, (c) 2 00 , 3 00 , … for the alkyl groups bound to N-1 of the indole/indazole fragment. NMR results for compounds 1, 5 and 6 have not been reported before.…”

“…STS-135 (8) was detected and chemically characterized earlier and is a known ingredient in herbal smoking blends on the German market [13]. 5-Fluoro-AB-PINACA (1) was recently detected in Japan in herbal preparations containing larger amounts of another active ingredient, diphenidine, a dissociative anesthesia drug [14], and has been characterized by EI-and ESI-MS methods.…”

Metabolic characterization of (1-(5-fluoropentyl)-1H-indol-3-yl)(4-methyl-1-naphthalenyl)-methanone (MAM-2201) using human liver microsomes and cDNA-overexpressed cytochrome P450 enzymes

“…Structure-activity relationships for synthetic cannabinoids have been established [4][5][6][7][8], and JWH compounds (JWH-018, JWH-122, and JWH-073) have been modified as follows: introduction of a fluorine atom (AM-2201, MAM-2201, and EAM-2201) [9] and substitution of the naphthyl group for a cyclopropyl group (UR-144 and XLR-11) [10,11], adamantyl group (APICA and 5F-APICA) [10], or quinolinyl group (QUPIC and QUCHIC) [12,13]. Synthetic cannabinoids have been found in seized herbal materials, and their continual emergence on recreational and illicit drug markets has become a global issue [14][15][16][17][18][19].…”

“…MAM-2201, [1-(5-fluoropentyl)-1H-indol-3-yl](4-methyl-1-naphthalenyl)-methanone, is a third-generation synthetic cannabinoid detected as an active ingredient in illegal herbal incense blends [10,16,18,20,21]. MAM-2201 exerts potent pharmacological actions on brain function and causes psychoactive and intoxicating effects [22][23][24].…”

“…Possible metabolic pathways of MAM-2201 in human liver microsomes Cl int values for the formation of hydroxy-MAM-2201 (M1), N-(5-hydroxypentyl)-MAM-2201 (M13), and hydroxy-M13 (M14)(19,731,18,059, and 13,125 nL/min/ mg protein, respectively) were higher than Cl int values of the other 16 metabolites (32-1881 nL/min/mg protein) in human liver microsomes. These results indicate that hydroxylation to M1, oxidative defluorination to M13, and hydroxylation of M13 to M14 were the major metabolic pathways of MAM-2201 in human liver microsomes.…”