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

@article{Diao2018MetabolismOT,
  title={Metabolism of the new synthetic cannabinoid EG-018 in human hepatocytes by high-resolution mass spectrometry},
  author={Xingxing Diao and Jeremy Carlier and Mingshe Zhu and Marilyn A. Huestis},
  journal={Forensic Toxicology},
  year={2018},
  volume={36},
  pages={304-312}
}
PurposeThe present study aims to recommend appropriate urinary marker metabolites for documenting EG-018 consumption by investigating its metabolism in human hepatocytes.MethodsFor 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.ResultsEG-018 was highly metabolized in human hepatocytes. A total of eight metabolites were… 

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

The fungal model demonstrated its ability to be an independent in vitro model in synthetic cannabinoid metabolism research 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.

Phase I Metabolism of Synthetic Cannabinoid Receptor Agonist PX-1 (5F-APP-PICA) via Incubation with Human Liver Microsomes and UHPLC-HRMS.

The determination of the in vitro Phase I metabolism of one such compound, PX-1 (5F-APP-PICA), and appropriate markers to demonstrate human consumption are provided, and three monohydroxylated metabolites specific to Px-1 were identified and are reported for the first time.

Synthetic cannabinoid receptor agonists and their human metabolites in sewage water: Stability assessment and identification of transformation products.

The majority of investigated SCRAs, excluding the selected human metabolites, was recalcitrant to microbial degradation in sewage systems over a period of 29 days, and among the ten newly identified TPs three could be considered as relevant markers and should be included into future WBE studies to gain further insight into use and prevalence ofSCRAs on the drug market.

In silico, in vitro, and in vivo human metabolism of acetazolamide, a carbonic anhydrase inhibitor and common “diuretic and masking agent” in doping

ACZ, ACZ-Cys, and N-acetyl-ACZ are proposed as specific biomarkers of ACZ intake in doping and urine samples from patients receiving a single 5.0 mg/kg BW PO ACZ dose were analyzed to confirm the results in vivo.

Saccharomyces cerevisiae as a model to study synthetic cannabinoids: the impact of using different carbon sources

It is suggested that glucose is the best carbon source to develop a yeast based toxicity sensor for SC, as yeast growth on glucose is more susceptible to EG-018, a similar SC that exerts an effect on glycolytic and pentose phosphate pathway at high concentrations of glucose.

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

Toxicity of synthetic cannabinoids is increasing along with the regulatory measures taken for their control

The results suggest that emerging modified SCs, to avoid the law, are becoming more toxic and dangerous, and it is time to rethink current legislation to prevent rise on public health issues derived from consumption of molecules of unknown toxicological profile.

Adding more "Spice" to the pot; a review of the chemistry and pharmacology of newly emerging heterocyclic synthetic cannabinoid receptor agonists.

This review highlights the importance of continued research in the field of SCRA chemistry and pharmacology, as recreational SCRA use remains a global public health issue and represents a serious control challenge for law enforcement agencies.

Interpol review of toxicology 2016–2019

Pyrrolidinyl Synthetic Cathinones α-PHP and 4F-α-PVP Metabolite Profiling Using Human Hepatocyte Incubations

The metabolite profile of two pyrrolidinyl SCs, α-PHP and 4F-α-PVP, were characterized to identify optimal intake markers and an additional major metabolite that might be crucial for documenting exposure to α- PHP is identified.

References

SHOWING 1-10 OF 41 REFERENCES

High-Resolution Mass Spectrometry for Characterizing the Metabolism of Synthetic Cannabinoid THJ-018 and Its 5-Fluoro Analog THJ-2201 after Incubation in Human Hepatocytes.

High-resolution mass spectrometry was used to identify optimal metabolite markers for laboratories to identify ThJ-018 and THJ-2201 intake and link observed adverse events to these new synthetic cannabinoids.

In vitro and in vivo human metabolism of a new synthetic cannabinoid NM-2201 (CBL-2201)

The present study aims to recommend appropriate marker metabolites by investigating NM-2201 metabolism in human hepatocytes, and to confirm the results in authentic human urine specimens, and recommends M13 (5-fluoro PB-22 3-carboxyindole) as a suitable urinary marker metabolite for confirming NM- 2201 and/or 5F-PB-22 intake.

In Vitro Metabolite Profiling of ADB-FUBINACA, A New Synthetic Cannabinoid

This is the first ADB-FUBINACA in vitro metabolism study; in vivo experiments enabling pharmacokinetic and pharmacodynamics studies or urine from authentic clinical/forensic cases are needed to confirm the results.

Approaches, Challenges, and Advances in Metabolism of New Synthetic Cannabinoids and Identification of Optimal Urinary Marker Metabolites

Novel SCs are incubated with human hepatocytes, the most abundant and characteristic metabolites are identified with high‐resolution mass spectrometry, and proposed hepatocyte marker metabolites are confirmed in authentic positive urine samples.

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.

Metabolic profiling of new synthetic cannabinoids AMB and 5F-AMB by human hepatocyte and liver microsome incubations and high-resolution mass spectrometry.

The metabolism of AMB and 5F-AMB is investigated and appropriate markers to identify their intake in clinical or forensic cases are proposed, providing valuable data for identifying these two novel psychoactive substances.

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.

Characteristics of the designer drug and synthetic cannabinoid receptor agonist AM-2201 regarding its chemistry and metabolism.

It is suggested that the amounts absorbed by smoking do not significantly influence the metabolic pattern in urine samples, and the N-(4-hydroxypentyl) metabolite of JWH-018 can serve as a valuable marker to distinguish consume of products containing AM-2201 from Jwh-018 use.

Detection of metabolites of the new synthetic cannabinoid CUMYL-4CN-BINACA in authentic urine samples and human liver microsomes using high-resolution mass spectrometry.

Urinary marker metabolites of CUMYL-4CN-BINACA are identified by investigating its metabolism in human liver microsomes and to confirm the results in authentic urine samples and recommend using M16, M8, and M11 as urinary marker metabolites to confirm CUMyl-4 CN-BinACA intake.

Phase I Hydroxylated Metabolites of the K2 Synthetic Cannabinoid JWH-018 Retain In Vitro and In Vivo Cannabinoid 1 Receptor Affinity and Activity

This study proposes that K2's high adverse effect occurrence is due, at least in part, to distinct JWH-018 metabolite activity at the cannabinoid 1 receptor (CB1R), and suggests that metabolites of most drugs, but not the carboxy metabolite, retain in vitro and in vivo activity at CB1Rs.