Forensic Toxicology

, Volume 36, Issue 2, pp 304–312 | Cite as

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

  • Xingxing Diao
  • Jeremy Carlier
  • Mingshe Zhu
  • Marilyn A. HuestisEmail author
Original Article



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


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.


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.


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.


EG-018 Synthetic cannabinoid Hepatocyte metabolism High-resolution mass spectrometry 



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

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


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Copyright information

© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2018

Authors and Affiliations

  • Xingxing Diao
    • 1
    • 2
  • Jeremy Carlier
    • 1
    • 3
  • Mingshe Zhu
    • 4
  • Marilyn A. Huestis
    • 1
    • 5
    Email author
  1. 1.Chemistry and Drug Metabolism, IRP, National Institute on Drug Abuse, National Institutes of HealthBaltimoreUSA
  2. 2.XenoBiotic Laboratories IncPlainsboroUSA
  3. 3.CIAN Diagnostics, LLCFrederickUSA
  4. 4.MassDefect TechnologiesPrincetonUSA
  5. 5.University of Maryland School of MedicineBaltimoreUSA

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