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

  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},
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… 

Phase I In Vitro Metabolic Profiling of the Synthetic Cannabinoid Receptor Agonists CUMYL-THPINACA and ADAMANTYL-THPINACA

In vitro phase I metabolic profiling was conducted of the two indazole-3-carboxamide SCRAs, suggesting that ADAMANTYL-THPINACA might be more prone to metabolic drug−drug interactions than CUMYL- THPINACA, when co-administrated with strong CYP3A4 inhibitors.

In vitro phase I metabolic profiling of the synthetic cannabinoids AM-694, 5F-NNEI, FUB-APINACA, MFUBINAC and AMB-FUBINACA.

Human liver microsome systems are used to study the in vitro phase I metabolic profiling of five synthetic cannabinoids, namely AM-694, 5F-NNEI, FUB-APINACA, MFUBINAC and AMB-FUBINACA.

Monitoring metabolism of synthetic cannabinoid 4F-MDMB-BINACA via high-resolution mass spectrometry assessed in cultured hepatoma cell line, fungus, liver microsomes and confirmed using urine samples

The in-vitro models presented proved useful in the exhaustive metabolism studies and HepG2 identified the major 4F-MDMB-BINACA ester hydrolysis metabolite, and C. elegans demonstrated the capacity to produce a wide variety of metabolites.

Systematic characterization of metabolic profiles of ingenol in rats by UPLC-Q/TOF-MS and NMR in combination with microbial biotransformation

The results revealed that C. elegans bio-110930 functioned as an appropriate model to mimic and prepare phase I metabolism of ingenol in vivo to a certain extent, and revealed that hydroxylation, oxygenation, sulfonation, and glucuronidation were the major metabolic pathways ofingenol.

Comprehensive Metabolic Profiling of Euphorbiasteroid in Rats by Integrating UPLC-Q/TOF-MS and NMR as Well as Microbial Biotransformation

This is the first systematic investigation into the in vivo metabolic pathways of euphorbiasteroid and the cytotoxicity of its metabolites, which will be beneficial for better predicting the metabolism profile of Euphorbiae semen in humans and understanding its possible toxic material basis.

In vitro and in vivo pharmacological evaluation of the synthetic cannabinoid receptor agonist EG-018

Recent bionalytical methods for the determination of new psychoactive substances in biological specimens.

The goal of this work is to perform a critical review regarding bionalytical methods that can be used for the determination of new psychoactive substances (phenylethylamines, cathinones, synthetic cannabinoids, opioids, benzodiazepines, etc), particularly concerning sample preparation techniques and associated analytical methods.

Phase I-metabolism studies of the synthetic cannabinoids PX-1 and PX-2 using three different in vitro models

PX-1 and PX-2 in vitro metabolites were revealed comprehensively by liquid chromatography–high-resolution mass spectrometry measurements and it is shown that all three in vitro assays are suitable for predicting metabolic pathways of synthetic cannabinoids.

Study on the metabolic process of synthetic cannabinoids 4F-MDMB-BINACA and 4F-MDMB-BICA in human liver microsome and zebrafish model via UHPLC-QE Orbitrap MS

These two structurally similar synthetic cannabinoids 4F-MDMB-BINACA and 4f-MD MB-BICA had similar metabolic processes, as well as similar structures of their main symbol metabolites.



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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

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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.