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Metabolism of Nine Synthetic Cannabinoid Receptor Agonists Encountered in Clinical Casework: Major in vivo Phase I Metabolites of AM-694, AM-2201, JWH-007, JWH-019, JWH-203, JWH-307, MAM-2201, UR-144 and XLR-11 in Human Urine Using LC-MS/MS

[ Vol. 19 , Issue. 2 ]

Author(s):

Melanie Hutter, Sebastian Broecker, Stefan Kneisel, Florian Franz, Simon D. Brandt and Volker Auwarter*   Pages 144 - 162 ( 19 )

Abstract:


Background: `Herbal mixtures` containing synthetic cannabinoid receptor agonists (SCRAs) are promoted as legal alternative to marihuana and are easily available via the Internet. Keeping analytical methods for the detection of these SCRAs up-to-date is a continuous challenge for clinicians and toxicologists due to the high diversity of the chemical structures and the frequent emergence of new compounds. Since many SCRAs are extensively metabolized, analytical methods used for urine testing require previous identification of the major metabolites of each compound.

Objective: The aim of this study was to identify the in vivo major metabolites of nine SCRAs (AM- 694, AM-2201, JWH-007, JWH-019, JWH-203, JWH-307, MAM-2201, UR-144, XLR-11) for unambiguous detection of a drug uptake by analysis of urine samples.

Method: Positive urine samples from patients of hospitals, detoxification and therapy centers as well as forensic-psychiatric clinics were analyzed by means of liquid chromatography-tandem mass spectrometry (LC-MS/MS) and liquid chromatography-quadrupole time-of-flight mass spectrometry (LCqToF- MS) for investigation of the major in vivo metabolites.

Results: For all investigated SCRAs, monohydroxylation, dihydroxylation and/or formation of the Nhexanoic/ pentanoic acid metabolites were among the most abundant metabolites detected in human urine samples. Substitution of the fluorine atom was observed to be an important metabolic reaction for compounds carrying an N-(5-fluoropentyl) side chain. N-Dealkylated metabolites were not detected in vivo.

Conclusion: The investigated metabolites facilitate the reliable detection of drug uptake by analysis of urine samples. For distinction between uptake of the fluorinated and the non-fluorinated analogs, the N-(4-hydroxypentyl) metabolite of the non-fluorinated analog was identified as a useful analytical target and consumption marker.

Keywords:

Synthetic cannabinoid receptor agonists, metabolism, LC-MS/MS, aminoalkylindoles, clinical toxicology, forensic toxicology.

Affiliation:

Institute of Forensic Medicine, Forensic Toxicology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Albertstr. 9, 79104 Freiburg, Broeckers Solutions, Dyrotzer Stra├če 8, 13583 Berlin, Institute of Forensic Medicine, Forensic Toxicology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Albertstr. 9, 79104 Freiburg, Institute of Forensic Medicine, Forensic Toxicology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Albertstr. 9, 79104 Freiburg, School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool L3 3AF, Institute of Forensic Medicine, Forensic Toxicology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Albertstr. 9, 79104 Freiburg

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