Abstract
A potent synthetic cannabinoid receptor agonist, JHW-018, was recently detected as one of the most prominent active agents in abusively used incenses such as Spice and other herbal blends. The high pharmacological and addictive potency of JWH-018 highlights the importance of elucidating the metabolism of JWH-018, without which a meaningful insight into its pharmacokinetics and its toxicity would not be possible. In the present study, the cytochrome P450 phase I metabolites of JWH-018 were investigated, after in vitro incubation of the drug with human liver microsomes, followed by liquid chromatography–tandem mass spectrometry analysis. This revealed monohydroxylation of the naphthalene ring system, the indole moiety, and the alkyl side chain. In addition, observations were made of dihydroxylation of the naphthalene ring system, and the indole moiety, or as result of a combination of monohydroxylations of both the naphthalene ring system and the indole moiety or the alkyl side chain, or a combination of monohydroxylations of both the indole ring system and the alkyl side chain. There is also evidence of trihydroxylation at different locations of the hydroxyl groups in the molecule. Furthermore, dehydration of the alkyl side chain, in combination with both monohydroxylation and dihydroxylation as well as arene oxidation of the naphthalene ring system, combined with both monohydroxylation and dihydroxylation at different sites of oxidation were found. N-dealkylation also in combination with both monohydroxylation and dihydrodiol formation of the N-dealkylated metabolite was detected. Finally, a metabolite was found carboxylated at the alkyl side chain.
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Abbreviations
- ESI:
-
Electrospray ionization
- HLM:
-
Human liver microsome
- HPLC:
-
High-performance liquid chromatography
- LC:
-
Liquid chromatography
- MRM:
-
Multiple reaction monitoring
- MS:
-
Mass spectrometry
- MS/MS:
-
Tandem mass spectrometry
- SPE:
-
Solid-phase extraction
- Δ9-THC:
-
Δ9-tetrahydrocannabinol
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Acknowledgements
The authors thank J.W. Huffmann, Clemson University, USA, for providing samples of JWH-018, Daniel Lenz for his scientific support, and June Mercer-Chalmers for proofreading this manuscript and fruitful discussions.
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Wintermeyer, A., Möller, I., Thevis, M. et al. In vitro phase I metabolism of the synthetic cannabimimetic JWH-018. Anal Bioanal Chem 398, 2141–2153 (2010). https://doi.org/10.1007/s00216-010-4171-0
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DOI: https://doi.org/10.1007/s00216-010-4171-0