Citation

Fabregat-Safont D, Mardal M, Noble C, Cannaert A, Stove CP, Sancho JV, Linnet K, Hernández F, Ibáñez M. Drug Test. Anal. 2019; ePub(ePub): ePub.

Affiliation

Research Institute for Pesticides and Water, University Jaume I, Avda. Sos Baynat s/n, 12071, Castellón, Spain.

Copyright

(Copyright © 2019, John Wiley and Sons)

DOI

10.1002/dta.2659

PMID

31192526

Abstract

Synthetic cannabinoids (SCs) represented 45% of the new psychoactive substances seizures in Europe (data from 2016). The consumption of SCs is an issue of concern due to the still unknown toxicity and effects on human health, the great variety of compounds synthetized and continuous modifications in their chemical structure to avoid regulatory issues. These compounds are extensively metabolised in the organism and therefore often cannot be detected as the intact molecule in human urine. For this reason, the monitoring of SCs in forensic samples must be performed by the analysis of its metabolites. In this work, a workflow for the comprehensive study of SC consumption is proposed and applied to 5F-APP-PICA (also known as PX 1 or SRF-30) and AMB-FUBINACA (also known as FUB-AMB or MMB-FUBINACA), based not only on the elucidation of their metabolites but also including functional data by the use of the NanoLuc approach, previously published. Both cannabinoids were completely metabolised by human hepatocytes (12 and 8 metabolites were elucidated by high resolution mass spectrometry for 5F-APP-PICA and AMB-FUBINACA, respectively) and therefore suitable consumption markers have been proposed. The bioassays revealed that 5F-APP-PICA presented lower activity than AMB-FUBINACA at CB1 and CB2 receptors, based on the half maximal effective concentration (EC₅₀ ) and the maximum response (E_max ). These results are in agreement with the different intoxication cases found in literature for AMB-FUBINACA.

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Language: en

Keywords

5F-APP-PICA; AMB-FUBINACA; Synthetic cannabinoids; high resolution mass spectrometry; metabolite identification