Metabolism of dipentylone in zebrafish and human liver microsomes determined by liquid chromatography-high resolution mass spectrometry

Yiling Tang; Linhao Xu; Junbo Zhao; Ping Xiang; Hui Yan

doi:10.1016/j.jpba.2023.115710

Metabolism of dipentylone in zebrafish and human liver microsomes determined by liquid chromatography-high resolution mass spectrometry

J Pharm Biomed Anal. 2023 Nov 30:236:115710. doi: 10.1016/j.jpba.2023.115710. Epub 2023 Sep 6.

Authors

Yiling Tang¹, Linhao Xu¹, Junbo Zhao², Ping Xiang², Hui Yan³

Affiliations

¹ Department of Forensic Toxicology, Academy of Forensic Science, Shanghai Key Laboratory of Forensic Medicine, Shanghai 200063, China; Department of Pharmaceutical Analysis, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
² Department of Forensic Toxicology, Academy of Forensic Science, Shanghai Key Laboratory of Forensic Medicine, Shanghai 200063, China.
³ Department of Forensic Toxicology, Academy of Forensic Science, Shanghai Key Laboratory of Forensic Medicine, Shanghai 200063, China. Electronic address: yanh501@163.com.

PMID: 37690187
DOI: 10.1016/j.jpba.2023.115710

Abstract

The consumption of novel psychoactive substances (NPS) is exceedingly prevalent in society, as these substances are sold and distributed as "legal highs." One novel synthetic cathinone emerging in the market is 1-(1,3-benzodioxol-5-yl)-2-(dimethylamino) pentan-1-one (dipentylone). The goal of this work was to study the in vivo and in vitro metabolism of dipentylone in zebrafish and human liver microsomes (HLMs) by liquid chromatography-high resolution mass spectrometry (LC-HRMS). The zebrafish and HLM samples contained 14 dipentylone metabolites, specifically 12 phase Ⅰ metabolites and 2 phase Ⅱ metabolites. The main metabolic pathways included monohydroxylation (M1 and M2), N-dealkylation (M3), hydroxylation of the aromatic ring and dealkoxylation of M3 (M4), O-dealkylation (M5), N-dealkylation of M5 (M6), reduction of carboxide (M7), monohydroxylation of M5 (M8), dehydrogenation (M9), dealkoxylation (M10), N-dealkylation of M10 (M11), dealkoxylation of M9 (M12), glucuronidation of M5 (M13), and sulfation (M14). The monohydroxylated metabolite (M2) can be recommended as metabolic markers for dipentylone. This study is the first to identify a target compound for monitoring the abuse of dipentylone and to determine the essential chemical structure of the metabolites for further toxicological research.

Keywords: Dipentylone; Human liver microsomes; Metabolism; Synthetic cathinone; Zebrafish.