Phase I metabolism of four amide synthetic cannabinoids in human liver microsomes

LIU Shengfeng; ZHANG Lan; LIU Shucheng; HOU Chenzhi; XU Peng; DI Bin

doi:10.11665/j.issn.1000-5048.20220508

Journal of China Pharmaceutical University > 2022 > 53(5): 577-590. > DOI: 10.11665/j.issn.1000-5048.20220508

LIU Shengfeng, ZHANG Lan, LIU Shucheng, HOU Chenzhi, XU Peng, DI Bin. Phase I metabolism of four amide synthetic cannabinoids in human liver microsomes[J]. Journal of China Pharmaceutical University, 2022, 53(5): 577-590. DOI: 10.11665/j.issn.1000-5048.20220508

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Phase I metabolism of four amide synthetic cannabinoids in human liver microsomes

LIU Shengfeng^1,2,
ZHANG Lan^1,2,
LIU Shucheng^1,2,
HOU Chenzhi^1,2,
XU Peng^2,3,
DI Bin^1,2

1.
Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009
2.
China National Narcotics Control Commission-China Pharmaceutical University Joint Laboratory on Key Technologies of Narcotics Control, Nanjing 210009
3.
Key Laboratory of Drug Monitoring and Control, Drug Intelligence and Forensic Center, Ministry of Public Security, Beijing 100193, China

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Received Date: March 23, 2022
Revised Date: September 13, 2022

Graphical Abstract

Abstract

Abstract

This study was performed to determine the metabolic profile of four amide synthetic cannabinoids that recently abused, i.e., ADB-4en-PINACA, 4CN-CUMYL-BUTINACA, 5F-EMB-PICA and 4F-MDMB-BUTICA, in human liver microsomes (HLMs). The four amide synthetic cannabinoids were added to the microsomal incubation model, being incubated for 10 min, 60 min or 3 h to simulate human hepatic metabolism.Liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) analytical instrument was employed to determine and speculate the structure of phase I metabolites and their possible metabolic pathways.The results showed that there were 27 phase I metabolic pathways for the four amide synthetic cannabinoids, including hydroxylation, carboxylation, N-dealkylation and ester hydrolysis, with the main phase I metabolic pathways of ester hydrolysis, dihydrodiol (pentenyl tail), oxidative defluorination to carboxylic acid, monohydroxylation (alkyl side chain or indole/indazole ring) and N-dealkylation.The results of this study may provide potential detection markers for forensic identification and sewage abuse assessment of the four amide synthetic cannabinoids.
- amide synthetic cannabinoids,
- human liver microsomes,
- phase I metabolism,
- metabolic profile,
- ADB-4en-PINACA,
- 4CN-CUMYL-BUTINACA,
- 5F-EMB-PICA,
- 4F-MDMB-BUTICA

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References

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