title: Detection of the recently emerged synthetic cannabinoid 5F-MDMB-PICA in 'legal high' products and human urine samples.
abstract: Indole or indazole-based synthetic cannabinoids (SCs) bearing substituents derived from valine or tert-leucine are frequently abused new psychoactive substances (NPS). The emergence of 5F-MDMB-PICA (methyl N-{[1-(5-fluoropentyl)-1H-indol-3-yl]carbonyl}-3-methylvalinate) on the German drug market is a further example of a substance synthesized in the context of scientific research being misused by clandestine laboratories by adding it to 'legal high' products. In this work, we present the detection of 5F-MDMB-PICA in several legal high products by gas chromatography-mass spectrometry (GC-MS) analysis. To detect characteristic metabolites suitable for a proof of 5F-MDMB-PICA consumption by urine analysis, pooled human liver microsome (pHLM) assays were performed and evaluated using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QToF-MS) techniques to generate reference spectra of the in vitro phase I metabolites. The in vivo phase I metabolism was investigated by the analysis of more than 20 authentic human urine specimens and compared to the data received from the pHLM assay. Biotransformation of the 5-fluoropentyl side chain and hydrolysis of the terminal methyl ester bond are main phase I biotransformation steps. Two of the identified main metabolites formed by methyl ester hydrolysis or mono-hydroxylation at the indole ring system were evaluated as suitable urinary biomarkers and discussed regarding the interpretation of analytical findings. Exemplary analysis of one urine sample for 5F-MDMB-PICA phase II metabolites showed that two of the main phase I metabolites are subject to extensive glucuronidation prior to renal excretion. Therefore, conjugate cleavage is reasonable for enhancing sensitivity. Commercially available immunochemical pre-tests for urine proved to be unsuitable for the detection of 5F-MDMB-PICA consumption. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: Institute of Forensic Medicine, Forensic Toxicology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Albertstr. 9, 79104, Freiburg, Germany.
authors.forename: Lukas
authors.initials: L
authors.lastname: Mogler
authors.affiliation: Institute of Forensic Medicine, Forensic Toxicology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Albertstr. 9, 79104, Freiburg, Germany.|Hermann Staudinger Graduate School, University of Freiburg, Hebelstraße 27, 79104, Freiburg, Germany.
authors.forename: Florian
authors.identifier: http://orcid.org/0000-0001-6158-2882
authors.initials: F
authors.lastname: Franz
authors.affiliation: Institute of Forensic Medicine, Forensic Toxicology, Medical Center - University of Rostock, St.-Georg-Str. 108, 18055, Rostock, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Rentsch
authors.affiliation: Institute of Forensic Medicine, Forensic Toxicology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Albertstr. 9, 79104, Freiburg, Germany.|Hermann Staudinger Graduate School, University of Freiburg, Hebelstraße 27, 79104, Freiburg, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Angerer
authors.affiliation: Clinical Chemistry Laboratory, medbo® - District Hospital for Mental Health, Universitätstraße 84, 93053, Regensburg, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Weinfurtner
authors.affiliation: School of Chemistry, The University of Sydney, Eastern Avenue, NSW, 2006, Australia.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Longworth
authors.affiliation: Department of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, Lane 235, Stanford, CA, 94305, USA.
authors.forename: Samuel D
authors.identifier: http://orcid.org/0000-0002-4690-4318
authors.initials: SD
authors.lastname: Banister
authors.affiliation: School of Chemistry, The University of Sydney, Eastern Avenue, NSW, 2006, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Kassiou
authors.affiliation: Institute of Forensic Medicine, Forensic Toxicology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Albertstr. 9, 79104, Freiburg, Germany.
authors.forename: Bjoern
authors.initials: B
authors.lastname: Moosmann
authors.affiliation: Institute of Forensic Medicine, Forensic Toxicology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Albertstr. 9, 79104, Freiburg, Germany.
authors.forename: Volker
authors.identifier: http://orcid.org/0000-0002-1883-2804
authors.initials: V
authors.lastname: Auwärter
mesh_terms: D002186:Cannabinoids / Q000737:chemistry / Q000378:metabolism / Q000652:urine*; D002853:Chromatography, Liquid / Q000379:methods / Q000592:standards; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods* / Q000592:standards; D006801:Humans; D013287:Illicit Drugs / Q000737:chemistry / Q000378:metabolism / Q000652:urine*; D008862:Microsomes, Liver / Q000378:metabolism*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D016482:Urinalysis / Q000379:methods / Q000592:standards
chemical_list: D002186:Cannabinoids; D013287:Illicit Drugs
keywords: 5F-ADBICA; 5F-PB-22; consumption marker; metabolism; new psychoactive substances