International Journal of Legal Medicine

, Volume 133, Issue 4, pp 1049–1064 | Cite as

Phase I metabolic profiling of the synthetic cannabinoids THJ-018 and THJ-2201 in human urine in comparison to human liver microsome and cytochrome P450 isoenzyme incubation

  • Franziska Gaunitz
  • Andreas Thomas
  • Mathias Fietzke
  • Florian Franz
  • Volker Auwärter
  • Mario Thevis
  • Katja Mercer-Chalmers-BenderEmail author
Original Article


Despite the increasing relevance of synthetic cannabinoids as one of the most important classes within “New Psychoactive Substances”, there is still a lack of knowledge concerning their metabolism in humans. Due to the extensive metabolism of synthetic cannabinoids, metabolites are necessarily the best target analytes in urine, posing additional challenges to forensic analysis. The aims of this study were to identify appropriate urinary targets indicating intake of THJ-018 or THJ-2201 as well as to elucidate the most important cytochrome P450 isoenzymes within the metabolism of THJ-018 and THJ-2201 in vitro. For this purpose, the in vitro metabolism of THJ-018 and THJ-2201 was initially established using pooled human liver microsomes. The results obtained were compared to previously published in vitro results as well as to the results of the metabolic profiles from selected recombinant cytochrome P450 isoenzymes and from 23 urine samples from forensic cases. LC-HRMS was used to conduct product ion scans and to examine the metabolite spectra. For THJ-018, 17 different metabolite groups containing 33 different metabolites and isomers were detected after microsomal incubation, with the major metabolic pathways being monohydroxylation at the pentyl chain and of the naphthyl moiety as well as dihydroxylation of both residues. For THJ-2201, 19 different metabolite groups and 46 different metabolites and isomers were observed. The major metabolic pathways were monohydroxylation at the naphthyl moiety and oxidative defluorination. Significant contribution to the in vitro metabolism of THJ-018 and THJ-2201 originated from CYP2B6, CYP2C19, CYP3A4, and CYP3A5. As several cytochrome P450 isoenzymes are involved in the metabolism of these synthetic cannabinoids, a co-consumption with other drugs is unlikely to have an impact on their metabolism.


Synthetic cannabinoids THJ-018 THJ-2201 Phase I metabolism Urine CYP isoforms 



Special thanks are directed to June Mercer-Chalmers-Bender for English language editing. The authors also thank Hilke Andresen-Streichert for her support.

Funding information

This work was funded by the German Federal Ministry for Economic Affairs and Energy and the Central innovation program for medium-sized companies, respectively (grant number KF2429613MD3). An additional financial support also came from the German B.A.D.S. (Bund gegen Alkohol und Drogen im Straßenverkehr; Union against Alcohol and Drugs in Road Transport).

Compliance with ethical standards

Compliance with the law

All experiments comply with the current laws of the Federal Republic of Germany.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

414_2018_1964_MOESM1_ESM.docx (30 kb)
ESM 1 (DOCX 29 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Franziska Gaunitz
    • 1
  • Andreas Thomas
    • 2
  • Mathias Fietzke
    • 1
  • Florian Franz
    • 3
    • 4
  • Volker Auwärter
    • 3
  • Mario Thevis
    • 2
  • Katja Mercer-Chalmers-Bender
    • 1
    • 5
    Email author
  1. 1.Institute of Legal Medicine, Faculty of MedicineUniversity of CologneCologneGermany
  2. 2.Institute of BiochemistryGerman Sport University CologneCologneGermany
  3. 3.Institute of Forensic Medicine, Medical Center – University of Freiburg, Faculty of MedicineUniversity of FreiburgFreiburgGermany
  4. 4.Hermann Staudinger Graduate SchoolUniversity of FreiburgFreiburgGermany
  5. 5.Institute of Forensic Medicine, Health Department Basel-Stadt, SwitzerlandUniversity of BaselBaselSwitzerland

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