N-Ethylpentedrone: first hair detection and human metabolic profiling across multiple biological matrices using UHPLC-HRMS, molecular networking and in silico prediction
Abstract
N-ethylpentedrone (NEP) is a New Psychoactive Substance (NPS) of the cathinone class that has raised public health concerns, scheduled by both the United Nations Office on Drugs and Crime and the European Union Drugs Agency, since 2024. We report here a fatal case involving a 29-years-old man who used NEP in a chemsex context. Three plastic bags containing off-white to beige powders and crystals were found near the body. Proton and carbon nuclear magnetic resonance spectrometry (1H and 13C NMR) and ultra-high performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) analyses confirmed all three bags contained NEP with purity above 98%. UHPLC-HRMS data analyses using molecular networking and in silico prediction allowed to propose NEP metabolic profile in peripheral and cardiac blood, bile, gastric fluid, urine and hair. We described here six Phase I metabolites, and we proposed NEP (C13H19NO) as the principal biomarker in NEP intake, metabolites M4 (C11H17NO) and M1 (C11H15NO) serving as biomarkers of consumption, as all of which were detected in all postmortem body fluid samples as well as in hair. Predominant metabolic pathways involved keto-reduction, N-dealkylation, hydroxylation, and oxidation, while no Phase II metabolites were detected under the applied analytical conditions. NEP was quantified at 18 mg/L and 20 mg/L in peripheral and cardiac blood, respectively, and 654-755 pg/mg in hair. These exceptionally high concentrations in biological fluids indicate an acute NEP intoxication, while hair analyses confirm repeated exposure over several months, consistent with chronic use. In summary, the identification of these metabolites in various postmortem body fluid matrices and in hair will improve our understanding of potential drug consumption markers and contribute to better monitoring and detection of N-ethylpentedrone use and abuse.
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BibTeX
@article{pasquet2026nethylpentedrone,
title = {{N-Ethylpentedrone: first hair detection and human metabolic profiling across multiple biological matrices using UHPLC-HRMS, molecular networking and in silico prediction}},
author = {Agathe Pasquet and Romain Pelletier and Roxane Rouah and Tania Panter and Mélanie Loiseau and François-Hugues Porée and Thomas Gicquel and Pascal Guerard},
journal = {Archives of Toxicology},
year = {2026},
month = jun,
doi = {10.1007/s00204-026-04412-0},
url = {https://hal.science/hal-05645924v1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - N-Ethylpentedrone: first hair detection and human metabolic profiling across multiple biological matrices using UHPLC-HRMS, molecular networking and in silico prediction
AU - Agathe Pasquet
AU - Romain Pelletier
AU - Roxane Rouah
AU - Tania Panter
AU - Mélanie Loiseau
AU - François-Hugues Porée
AU - Thomas Gicquel
AU - Pascal Guerard
PY - 2026
DA - 2026/06/02
JO - Archives of Toxicology
DO - 10.1007/s00204-026-04412-0
UR - https://hal.science/hal-05645924v1
AB - N-ethylpentedrone (NEP) is a New Psychoactive Substance (NPS) of the cathinone class that has raised public health concerns, scheduled by both the United Nations Office on Drugs and Crime and the European Union Drugs Agency, since 2024. We report here a fatal case involving a 29-years-old man who used NEP in a chemsex context. Three plastic bags containing off-white to beige powders and crystals were found near the body. Proton and carbon nuclear magnetic resonance spectrometry (1H and 13C NMR) and ultra-high performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) analyses confirmed all three bags contained NEP with purity above 98%. UHPLC-HRMS data analyses using molecular networking and in silico prediction allowed to propose NEP metabolic profile in peripheral and cardiac blood, bile, gastric fluid, urine and hair. We described here six Phase I metabolites, and we proposed NEP (C13H19NO) as the principal biomarker in NEP intake, metabolites M4 (C11H17NO) and M1 (C11H15NO) serving as biomarkers of consumption, as all of which were detected in all postmortem body fluid samples as well as in hair. Predominant metabolic pathways involved keto-reduction, N-dealkylation, hydroxylation, and oxidation, while no Phase II metabolites were detected under the applied analytical conditions. NEP was quantified at 18 mg/L and 20 mg/L in peripheral and cardiac blood, respectively, and 654-755 pg/mg in hair. These exceptionally high concentrations in biological fluids indicate an acute NEP intoxication, while hair analyses confirm repeated exposure over several months, consistent with chronic use. In summary, the identification of these metabolites in various postmortem body fluid matrices and in hair will improve our understanding of potential drug consumption markers and contribute to better monitoring and detection of N-ethylpentedrone use and abuse.
SN - 0340-5761
SN - 0340-5761
ER -