Document Type
Article
Publication Date
2-9-2024
Abstract
New Psychoactive Substances (NPSs) are defined as a group of substances produced from molecular modifications of traditional drugs. These molecules represent a public health problem since information about their metabolites and toxicity is poorly understood. N-ethyl pentedrone (NEP) is an NPS that was identified in the illicit market for the first time in the mid-2010s, with four intoxication cases later described in the literature. This study aims to evaluate the metabolic stability of NEP as well as to identify its metabolites using three liver microsomes models. To investigate metabolic stability, NEP was incubated with rat (RLM), mouse (MLM) and human (HLM) liver microsomes and its concentration over time evaluated by liquid chromatography–mass spectrometry. For metabolite identification, the same procedure was employed, but the samples were analyzed by liquid chromatography–high resolution mass spectrometry. Different metabolism profiles were observed depending on the model employed and kinetic parameters were determined. The in vitro NEP elimination half-lives (t1/2) were 12.1, 187 and 770 min for the rat, mouse and human models, respectively. Additionally, in vitro intrinsic clearances (Cl int, in vitro) were 229 for rat, 14.8 for mouse, and 3.6 μL/min/mg in the human model, and in vivo intrinsic clearances (Cl int, in vivo) 128, 58.3, and 3.7 mL/min/kg, respectively. The HLM model had the lowest rate of metabolism when compared to RLM and MLM. Also, twelve NEP metabolites were identified from all models, but at different rates of production.
Recommended Citation
Godoi, Alexandre Barcia; Antunes, Natalícia de Jesus; Cunha, Kelly Francisco; Martins, Aline Franco; Huestis, Marilyn A.; and Costa, Jose Luiz, "Metabolic Stability and Metabolite Identification of N-Ethyl Pentedrone Using Rat, Mouse and Human Liver Microsomes" (2024). Institute of Emerging Health Professions Faculty Papers. Paper 26.
https://jdc.jefferson.edu/iehpfp/26
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Language
English
Comments
This article is the author's final published version in Pharmaceutics, Volume 16, Issue 2, February 2024, Article number 257.
The published version is available at https://doi.org/10.3390/pharmaceutics16020257.
Copyright © 2024 by the authors