Identification of a new tert -leucinate class synthetic cannabinoid in powder and “spice-like” herbal incenses: Methyl 2-[[1-(5-fluoropentyl)indole-3-carbonyl]amino]-3,3-dimethyl-butanoate (5F-MDMB-PICA)

Abstract

A brown powder and different product packages of "spice-like" herbal incenses were analyzed using a systematic identification approach based on liquid chromatography with diode array detector (HPLC-PDA) and gas chromatography mass spectrometry (GC-MS) with computer based library search against spectral libraries. However, the most predominant compound in the methanolic sample solutions could not be identified. In order to elucidate the chemical structure, a more extensive analysis of the material was initiated using liquid chromatography mass spectrometry (LC-MS), electrospray high resolution mass spectrometry (ESI-HRMS) and H,C and F nuclear magnetic resonance spectroscopy (NMR), which allowed the identification and characterization of the major compound as methyl 2-[[1-(5-fluoropentyl)indole-3-carbonyl]amino]-3,3-dimethyl-butanoate (5F-MDMB-PICA). The goal of this study is to provide analytical information for the identification of this new tert-leucinate class synthetic cannabinoid by various analytical methods.

Application of an activity‐based receptor bioassay to investigate the in vitro activity of selected indole‐ and indazole‐3‐carboxamide‐based synthetic cannabinoids at CB1 and CB2 receptors

“…5F‐AMB‐PICA (or MMB‐2201) (methyl (2S)‐2‐{[1‐(5‐fluoropentyl)‐1H‐indole‐3‐carbonyl]amino}‐3‐methylbutanoate) ( 6 ) is an indole‐3‐carboxamide derivative notified to the EMCDDA in 2014 and it is the 5‐fluoropentyl analog of AMB‐PICA . 5F‐MDMB‐PICA methyl (2S)‐2‐{[1‐(5‐fluoropentyl)‐1H‐indole‐3‐carbonyl]amino}‐3,3‐dimethylbutanoate) ( 7 ) was found in a seized herbal mixture in Belgium in 2017 and it had been synthesized before in 2015 . Furthermore, this drug was detected in human urine samples in Germany in 2017 .…”

Phase I metabolism of synthetic cannabinoid receptor agonist PX‐1 (5F‐APP‐PICA) via incubation with human liver microsomes and UHPLC–HRMS

“…Other synthetic cannabinoids containing fluoropentyl side chains whose in vitro and/or in vivo metabolic profile has been reported include AM‐2201, 5F‐ADB, 5F‐MDMB‐PICA, EG‐2201, and 5F‐CUMYL‐PEGACLONE (Figure ; Center for Forensic Science Research and Education, , ; Chimalakonda et al, ; Diao, Carlier, Zhu, & Huestis, ; Ernst, Langer, Bockelmann, Salkhordeh, & Beuerle, ; Hutter et al, ; Jang et al, ; Mogler et al, ; Mogler, Halter, Wilde, Franz, & Auwärter, ; Risseeuw et al, ; Sobolevsky et al, ; Yeter & Erol Öztürk, ). Structural differences exist between these compounds and PX‐1.…”

“…It is likely that 5F Research andEducation, 2019c, 2019d;Chimalakonda et al, 2012;Diao, Carlier, Zhu, & Huestis, 2018;Ernst, Langer, Bockelmann, Salkhordeh, & Beuerle, 2019;Hutter et al, 2013;Jang et al, 2014;Mogler et al, 2018;Mogler, Halter, Wilde, Franz, & Auwärter, 2019;Risseeuw et al, 2017;Sobolevsky et al, 2012;Yeter & Erol Öztürk, 2019). Structural differences exist between these compounds and PX-1.…”

Chemical profiling of the synthetic cannabinoid MDMB‐CHMICA: Identification, assessment, and stability study of synthesis‐related impurities in seized and synthesized samples

“…Compound I13 was identified as 5F‐MDMB‐PICA which itself is a synthetic cannabinoid which was first detected on the European market in 2016 . The main difference to 1 is the substitution of the N‐linked cyclohexylmethyl group with a 5‐fluoropentyl chain, which is a common aliphatic residue for various synthetic cannabinoids already on the market (eg, 5F‐PB‐22, Cumyl‐5F‐PINACA).…”

“…44,45 Since the terminal amino acid in I12 is present as the methyl ester, the epimerization over a DKP must take place before or during the ester- Compound I13 was identified as 5F-MDMB-PICA which itself is a synthetic cannabinoid which was first detected on the European market in 2016. 47 The main difference to 1 is the substitution of the N- A link between tert-leucine and 2-aminobutyric acid is the industrial production of these non-proteinogenic amino acids which involves similar multienzyme processes. 49,50 Once the general technology has been established at a given site, the producer can extend its portfolio from one amino acid to the other relatively easily and at least one example of dual production within an otherwise very limited product portfolio is known.…”