In vitro metabolic profiling of synthetic cannabinoids by pooled human liver microsomes, cytochrome P450 isoenzymes, and Cunninghamella elegans and their detection in urine samples

@article{Gaunitz2019InVM,
  title={In vitro metabolic profiling of synthetic cannabinoids by pooled human liver microsomes, cytochrome P450 isoenzymes, and Cunninghamella elegans and their detection in urine samples},
  author={Franziska Gaunitz and Patrick Dahm and Lukas Mogler and Andreas Thomas and Mario Thevis and Katja Mercer-Chalmers-Bender},
  journal={Analytical and Bioanalytical Chemistry},
  year={2019},
  volume={411},
  pages={3561-3579}
}
AbstractAs synthetic cannabinoids are extensively metabolized, there is an urgent need for data on which metabolites can be used for successful urine screening. This study examines the in vitro metabolism of EG-018 and its 5F-analogue EG-2201 by means of comparing three different in vitro models: pooled human liver microsomes, cytochrome P450 isoenzymes, and a fungal approach utilizing the filamentous fungus Cunninghamella elegans LENDNER, which is known for its ability to mimic human… 

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References

SHOWING 1-10 OF 50 REFERENCES

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

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 these synthetic cannabinoids in vitro.

Comparative studies on the cytochrome p450-associated metabolism and interaction potential of selegiline between human liver-derived in vitro systems.

None of the techniques alone was able to predict all aspects of the metabolic and kinetic behavior of selegiline in vivo, however, when used as an integrated package, all significant characteristics were predictable.

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

The primary metabolites of EG-018 in human hepatocyte incubation were pentyl hydroxylated EG-18 (M6) and pentyl carbonylated EG-2018 (M8) and these two metabolites are proposed as the best urinary markers for confirming EG-019 intake.

Cytochrome P450-Mediated Oxidative Metabolism of Abused Synthetic Cannabinoids Found in K2/Spice: Identification of Novel Cannabinoid Receptor Ligands

Test the hypothesis that JWH-018 and its fluorinated counterpart AM2201 are subject to cytochrome P450 (P450)-mediated oxidation, forming potent hydroxylated metabolites that retain significant affinity and activity at the cannabinoid 1 (CB1) receptor.

Determination of AM-2201 metabolites in urine and comparison with JWH-018 abuse

The presence of 6-indole hydroxylated metabolites of each drug and N-4-hydroxy metabolite of AM-2201 was found to contribute to the decisive differences in the metabolic patterns of the two drugs.

Detection of urinary metabolites of AM-2201 and UR-144, two novel synthetic cannabinoids.

In vitro and in vivo metabolism of AM-2201 and forensic urine samples were analyzed and it has been shown that for both cannabimimetics the recommended screening targets are the monohydroxylated metabolites.