In Vitro Metabolism of 25B-NBF, 2-(4-Bromo-2,5-Dimethoxyphenyl)-N-(2-Fluorobenzyl)ethanamine, in Human Hepatocytes Using Liquid Chromatography⁻Mass Spectrometry.

Ju-Hyun Kim,Joo Lee,Sangwhan In,Yong-Yeon Cho,Sunjoo Kim,Jaesin Lee,Han Kang,Hye Lee

doi:10.3390/molecules24040818

Abstract

25B-NBF, 2-(4-bromo-2,5-dimethoxyphenyl)-N-(2-fluorobenzyl)ethanamine, is a new psychoactive substance classified as a phenethylamine. It is a potent agonist of the 5-hydroxytryptamine receptor, but little is known about its metabolism and elimination properties since it was discovered. To aid 25B-NBF abuse screening, the metabolic characteristics of 25B-NBF were investigated in human hepatocytes and human cDNA-expressed cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) enzymes using liquid chromatography–high resolution mass spectrometry. At a hepatic extraction ratio of 0.80, 25B-NBF was extensively metabolized into 33 metabolites via hydroxylation, O-demethylation, bis-O-demethylation, N-debenzylation, glucuronidation, sulfation, and acetylation after incubation with pooled human hepatocytes. The metabolism of 25B-NBF was catalyzed by CYP1A1, CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2J2, CYP3A4, and UGT2B7 enzymes. Based on these results, it is necessary to develop a bioanalytical method for the determination of not only 25B-NBF but also its metabolites in biological samples for the screening of 25B-NBF abuse.

Highlights

New psychoactive substances (NPSs) are abused compounds with effects similar to those of controlled drugs such as cannabis, morphine, cocaine, and amphetamine-type stimulants
Synthetic cannabinoids remain the most commonly abused group, recently phenethylamine abuse has been on the rise, accounting for 28.4% of cases of NPS abuse at the end of 2017 according to the United Nations Office on Drugs and Crime (UNODC) [1]
25B-NBF was extensively metabolized into 33 metabolites by hydroxylation, O-demethylation, bis-O-demethylation, N-dearylation, cysteine conjugation, glucuronidation, sulfation, and acetylation alone or in combination in human hepatocytes. 2C-B, one of the most widespread NPSs, was identified as a major metabolite of 25B-NBF

Summary

Introduction

New psychoactive substances (NPSs) are abused compounds with effects similar to those of controlled drugs such as cannabis, morphine, cocaine, and amphetamine-type stimulants. Since the United Nations Office on Drugs and Crime (UNODC) launched the international NPS monitoring system in 2009, the amount of NPSs has increased by 3.7 times to 479 substances in 2017 [1]. 620 NPS at the end of 2016 and stated that more than 70% of these had been newly detected in the previous 5 years [2]. NPSs can be classified based on their chemical structure as synthetic cannabinoids, synthetic cathinones, tryptamines, phenethylamines, and others. Synthetic cannabinoids remain the most commonly abused group, recently phenethylamine abuse has been on the rise, accounting for 28.4% of cases of NPS abuse at the end of 2017 according to the UNODC [1].

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Discussion

Conclusion