Metabolism of synthetic cannabinoids PB-22 and its 5-fluoro analog, 5F-PB-22, by human hepatocyte incubation and high-resolution mass spectrometry

@article{Wohlfarth2014MetabolismOS,
  title={Metabolism of synthetic cannabinoids PB-22 and its 5-fluoro analog, 5F-PB-22, by human hepatocyte incubation and high-resolution mass spectrometry},
  author={Ariane Wohlfarth and Adarsh Gandhi and Shaokun Pang and Mingshe Zhu and Karl B. Scheidweiler and Marilyn A. Huestis},
  journal={Analytical and Bioanalytical Chemistry},
  year={2014},
  volume={406},
  pages={1763-1780}
}
AbstractBackgroundPB-22 (1-pentyl-8-quinolinyl ester-1H-indole-3-carboxylic acid) and 5F-PB-22 (1-(5-fluoropentyl)-8-quinolinyl ester-1H-indole-3-carboxylic acid) are new synthetic cannabinoids with a quinoline substructure and the first marketed substances with an ester bond linkage. No human metabolism data are currently available, making it difficult to document PB-22 and 5F-PB-22 intake from urine analysis, and complicating assessment of the drugs’ pharmacodynamic and toxicological… 
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Highly Influential Citations
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95 Citations

Pentylindole/Pentylindazole Synthetic Cannabinoids and Their 5-Fluoro Analogs Produce Different Primary Metabolites: Metabolite Profiling for AB-PINACA and 5F-AB-PINACA
TLDR
This work determined metabolic stability and metabolites of N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-pentyl-1H-indazole- 3-carboxamide (AB-PINACA) and 5-fluoro-AB- PINACA (5F-AB -PINACA), two new synthetic cannabinoids, and investigated if results were similar.
Metabolic profiling of synthetic cannabinoid 5F-ADB by human liver microsome incubations and urine samples using high-resolution mass spectrometry.
TLDR
The in vitro metabolism of 5F-ADB was investigated by using pooled human liver microsomes assay and liquid chromatography-high-resolution mass spectrometry (LC-HRMS) and identified 20 metabolites formed via ester hydrolysis, N-dealkylation, oxidative defluorination, hydroxylations, dehydrogenation, further oxidation to N-pentanoic acid and glucuronidation or a combination of these reactions in vitro.
In Vitro Metabolite Profiling of ADB-FUBINACA, A New Synthetic Cannabinoid.
TLDR
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.
Metabolic Profile of Synthetic Cannabinoids 5F-PB-22, PB-22, XLR-11 and UR-144 by Cunninghamella elegans
TLDR
C. elegans demonstrated the capacity to produce a wide variety of metabolites including some major human metabolites of XLR-11 and UR-144 at high abundance, showing the potential for metabolism of newly emerging synthetic cannabinoids.
Human urinary metabolite pattern of a new synthetic cannabimimetic, methyl 2-(1-(cyclohexylmethyl)-1H-indole-3-carboxamido)-3,3-dimethylbutanoate
A number of metabolites of a new synthetic cannabimimetic, which is a derivative of 2-(1-(cyclohexylmethyl)-1H-indole-3-carboxamido)-3,3-dimethylbutanoic acid, were identified in human urine. The…
Human Hepatocyte Metabolism of Novel Synthetic Cannabinoids MN-18 and Its 5-Fluoro Analog 5F-MN-18.
BACKGROUND In 2014, 2 novel synthetic cannabinoids, MN-18 and its 5-fluoro analog, 5F-MN-18, were first identified in an ongoing survey of novel psychoactive substances in Japan. In vitro…
High-resolution mass spectrometric metabolite profiling of a novel synthetic designer drug, N-(adamantan-1-yl)-1-(5-fluoropentyl)-1H-indole-3-carboxamide (STS-135), using cryopreserved human hepatocytes and assessment of metabolic stability with human liver microsomes.
TLDR
High-resolution mass spectrometry with software-assisted data mining identified 29 STS-135 metabolites, providing potential urinary targets to document STs-135 intake in clinical and forensic settings and potential candidates for pharmacological testing.
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.
TLDR
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.
Phase I metabolism of the carbazole-derived synthetic cannabinoids EG-018, EG-2201, and MDMB-CHMCZCA and detection in human urine samples.
TLDR
A metabolite mono-hydroxylated at the cyclohexyl methyl tail is considered the most suitable compound-specific consumption marker while a biotransformation product of mono-Hydroxylation in combination with hydrolysis of the terminal methyl ester function provides best sensitivity due to its high abundance.
Differentiation and identification of 5F-PB-22 and its isomers.
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