title: Metabolites of synthetic cannabinoids in hair--proof of consumption or false friends for interpretation?
abstract: The detection of drug metabolites in hair is widely accepted as a proof for systemic uptake of the drug, unless the metabolites can be formed as artefacts. However, regarding synthetic cannabinoids, not much is known about mechanisms of incorporation into hair. For a correct interpretation concerning hair findings of these compounds and their metabolites, it is necessary to identify the different routes of incorporation and to assess their contribution to analytical findings. This study presents the results of the LC-ESI-MS/MS analysis of an authentic hair sample taken from a patient with a known history of heavy consumption of synthetic cannabinoids. In the authentic hair sample, 5F-PB-22 and AB-CHMINACA as well as their main metabolites 5F-PB-22 3-carboxyindole, PB-22 5-OH-pentyl, and AB-CHMINACA valine were detected in all segments, comprising segments grown in a time period where the substances had not been distributed on the 'legal high' market. To enable interpretation of the results regarding the distribution of the detected analytes along the hair shaft, the stability of 5F-PB-22 and AB-CHMINACA in hair matrix and under thermal stress was assessed. The stability tests revealed that the three 'metabolites' are also formed in externally contaminated hair after storage of the samples under different conditions. In addition, 5F-PB-22 3-carboxyindole and AB-CHMINACA valine were identified as degradation products in smoke condensate. Therefore, interpretation of 'metabolite' findings of compounds comprising chemically labile amide/ester bonds or 5-fluoro-pentyl side chains should be carried out with utmost care, taking into account the different mechanisms of formation and incorporation into hair.
authors.affiliation: Institute of Forensic Medicine, Forensic Toxicology, Medical Center-University of Freiburg, Albertstraße 9, 79104, Freiburg, Germany.|Hermann Staudinger Graduate School, University of Freiburg, Hebelstraße 27, 79104, Freiburg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Franz
authors.affiliation: Institute of Forensic Medicine, Forensic Toxicology, Medical Center-University of Freiburg, Albertstraße 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: Poison Information Center, Center for Pediatrics and Adolescent Medicine, Medical Center-University of Freiburg, Mathildenstraße 1, 79106, Freiburg, Germany.
authors.forename: Maren
authors.initials: M
authors.lastname: Hermanns-Clausen
authors.affiliation: Institute of Forensic Medicine, Forensic Toxicology, Medical Center-University of Freiburg, Albertstraße 9, 79104, Freiburg, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Auwärter
authors.affiliation: Institute of Forensic Medicine, Forensic Toxicology, Medical Center-University of Freiburg, Albertstraße 9, 79104, Freiburg, Germany. bjoern.moosmann@uniklinik-freiburg.de.
authors.forename: Bjoern
authors.initials: B
authors.lastname: Moosmann
mesh_terms: D000293:Adolescent; D002186:Cannabinoids / Q000378:metabolism*; D002853:Chromatography, Liquid / Q000379:methods; D005260:Female; D006197:Hair / Q000378:metabolism*; D006801:Humans; D057230:Limit of Detection; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D002186:Cannabinoids
keywords: 5F-PB-22; AB-CHMINACA; External contamination; Hair analysis; LC-ESI-MS/MS; Stability