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Metabolism of the new synthetic cannabinoid EG-018 in human hepatocytes by high-resolution mass spectrometry

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Abstract

Purpose

The present study aims to recommend appropriate urinary marker metabolites for documenting EG-018 consumption by investigating its metabolism in human hepatocytes.

Methods

For metabolite profiling, 10 µM EG-018 was incubated in human hepatocytes for 3 h. Metabolite identification in hepatocyte samples was accomplished with high-resolution mass spectrometry via information-dependent data acquisition.

Results

EG-018 was highly metabolized in human hepatocytes. A total of eight metabolites were characterized, mainly generated from hydroxylation and carbonylation on the pentyl chain. Dihydrodiol formation, N-dealkylation, and glucuronidation of hydroxylated metabolites were the other major pathways.

Conclusions

The primary metabolites of EG-018 in human hepatocyte incubation were pentyl hydroxylated EG-018 (M6) and pentyl carbonylated EG-018 (M8). These two metabolites are proposed as the best urinary markers for confirming EG-018 intake.

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Acknowledgements

This research was supported by the Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health.

Author information

Author notes

  1. Xingxing Diao

    Present address: XenoBiotic Laboratories Inc, Plainsboro, NJ, 08536, USA

  2. Jeremy Carlier

    Present address: CIAN Diagnostics, LLC, Frederick, MD, 21703, USA

Authors and Affiliations

  1. Chemistry and Drug Metabolism, IRP, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, 21224, USA

    Xingxing Diao, Jeremy Carlier & Marilyn A. Huestis

  2. MassDefect Technologies, Princeton, NJ, 08543, USA

    Mingshe Zhu

  3. University of Maryland School of Medicine, Baltimore, MD, 21201, USA

    Marilyn A. Huestis

Authors
  1. Xingxing Diao
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  4. Marilyn A. Huestis
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Corresponding author

Correspondence to Marilyn A. Huestis.

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Diao, X., Carlier, J., Zhu, M. et al. Metabolism of the new synthetic cannabinoid EG-018 in human hepatocytes by high-resolution mass spectrometry. Forensic Toxicol 36, 304–312 (2018). https://doi.org/10.1007/s11419-018-0404-2

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  • DOI: https://doi.org/10.1007/s11419-018-0404-2

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