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

  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},
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… 
Pentylindole/Pentylindazole Synthetic Cannabinoids and Their 5-Fluoro Analogs Produce Different Primary Metabolites: Metabolite Profiling for AB-PINACA and 5F-AB-PINACA
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.
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.
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
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.
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.
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.
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.


First metabolic profile of XLR-11, a novel synthetic cannabinoid, obtained by using human hepatocytes and high-resolution mass spectrometry.
These are the first data defining major urinary targets of XLR-11 metabolism that could document XLR -11 intake in forensic and clinical investigations.
First Characterization of AKB-48 Metabolism, a Novel Synthetic Cannabinoid, Using Human Hepatocytes and High-Resolution Mass Spectrometry
Using human hepatocytes and TripleTOF mass spectrometry, 17 novel phase I and II AKB-48 metabolites are identified, products of monohydroxylation, dihydroxylations, or trihydroxyation on the aliphatic adamantane ring or N-pentyl side chain.
Identification of two new-type synthetic cannabinoids, N-(1-adamantyl)-1-pentyl-1H-indole-3-carboxamide (APICA) and N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide (APINACA), and detection of five synthetic cannabinoids, AM-1220, AM-2233, AM-1241, CB-13 (CRA-13), and AM-1248, as designer drugs in
Two new-type synthetic cannabinoids, N-(1-adamantyl)-1-pentyl-1H-indole-3-carboxamide (APICA, 1) and N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide (APINACA, 2), have been identified as designer
Identification of two new-type designer drugs, piperazine derivative MT-45 (I-C6) and synthetic peptide Noopept (GVS-111), with synthetic cannabinoid A-834735, cathinone derivative 4-methoxy-α-PVP, and phenethylamine derivative 4-methylbuphedrine from illegal products
Two new-type designer drugs, piperazine derivative MT-45 and synthetic peptide Noopept and synthetic cannabinoids A-834735 and QUPIC N-(5-fluoropentyl) analog (synonym: 5-fluoro-PB-22, 4), are identified in chemical and herbal products.
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.
Two new-type cannabimimetic quinolinyl carboxylates, QUPIC and QUCHIC, two new cannabimimetic carboxamide derivatives, ADB-FUBINACA and ADBICA, and five synthetic cannabinoids detected with a thiophene derivative α-PVT and an opioid receptor agonist AH-7921 identified in illegal products
We identified two new-type cannabimimetic quinolinyl carboxylates, quinolin-8-yl 1-pentyl-(1H-indole)-3-carboxylate (QUPIC, 1) and quinolin-8-yl 1-(cyclohexylmethyl)-1H-indole-3-carboxylate (QUCHIC,
Chromatography-mass spectrometry studies on the metabolism of synthetic cannabinoids JWH-018 and JWH-073, psychoactive components of smoking mixtures.
Identification of in vitro metabolites of JWH-015, an aminoalkylindole agonist for the peripheral cannabinoid receptor (CB2) by HPLC-MS/MS
The in vitro microsomal metabolism of JWH-015, a ligand that exhibits a high binding affinity at the peripheral cannabinoid receptor CB2, has been studied. A total of 22 metabolites were identified
Solid-phase extraction and quantitative measurement of omega and omega-1 metabolites of JWH-018 and JWH-073 in human urine.
The liquid chromatography tandem mass spectrometry procedure coupled with an automated solid-phase extraction procedure incorporating deuterium-labeled internal standards provides rapid resolution of the (ω)- and (ω-1) metabolites with adequate sensitivity, precision, and accuracy for trace analysis in human urine.