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Erschienen in: Forensic Toxicology 1/2020

27.06.2019 | Original Article

Toxicokinetic studies of the four new psychoactive substances 4-chloroethcathinone, N-ethylnorpentylone, N-ethylhexedrone, and 4-fluoro-alpha-pyrrolidinohexiophenone

verfasst von: Lea Wagmann, Sascha K. Manier, Niels Eckstein, Hans H. Maurer, Markus R. Meyer

Erschienen in: Forensic Toxicology | Ausgabe 1/2020

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Abstract

Purpose

The presented study aimed to elucidate the toxicokinetics of the four synthetic cathinones 4-chloroethcathinone (4-CEC), N-ethylnorpentylone (N-ethylpentylone, ephylone), N-ethylhexedrone (NEH), and 4-fluoro-alpha-pyrrolidinohexiophenone (4-fluoro-alpha-pyrrolidinohexanophenone, 4-F-α-PHP, 4F-alpha-PHP, 4F-PHP).

Methods

First, their metabolism was studied using human urine and blood samples. Analysis of specimens was performed by liquid chromatography-high resolution tandem mass spectrometry (LC-HRMS/MS) and gas chromatography–mass spectrometry (GC–MS). LC-HRMS/MS was also used to analyze in vitro incubations of the new psychoactive substances using pooled human liver S9 fraction (pS9), to identify the monooxygenases involved in the initial metabolic steps, and determination of plasma concentrations after a standard addition method. Metabolic stability was tested in pooled human liver microsomes incubations analyzed by LC-ion trap MS.

Results

Using LC-HRMS/MS, 47 metabolites in total were found in patient samples and pS9 incubations. Using GC–MS, 4-CEC, ephylone, NEH, and five of their metabolites were detectable in urine. The following main phase I reactions were observed: carbonyl group reduction, N-deethylation, hydroxylation, lactam formation (4F-PHP), and demethylenation (ephylone). Mainly glucuronidations were observed as phase II reactions besides conjugates with the dicarboxylic acids malonic, succinic, and glutaric acid (4-CEC), sulfation, methylation (both ephylone), and N-acetylation (NEH). A broad range of monooxygenases was involved in the initial steps with exception of NEH (only CYP1A2 and CYP2C19). 4F-PHP had the shortest in vitro half-life (38 min) and highest intrinsic clearance (15.7 mL/min/kg). Plasma concentrations ranged from 0.8 to 8.5 ng/mL.

Conclusions

Our results are expected to help toxicologists to reliably identify these substances in case of suspected abuse and allow them a thorough risk assessment.
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Metadaten
Titel
Toxicokinetic studies of the four new psychoactive substances 4-chloroethcathinone, N-ethylnorpentylone, N-ethylhexedrone, and 4-fluoro-alpha-pyrrolidinohexiophenone
verfasst von
Lea Wagmann
Sascha K. Manier
Niels Eckstein
Hans H. Maurer
Markus R. Meyer
Publikationsdatum
27.06.2019
Verlag
Springer Singapore
Erschienen in
Forensic Toxicology / Ausgabe 1/2020
Print ISSN: 1860-8965
Elektronische ISSN: 1860-8973
DOI
https://doi.org/10.1007/s11419-019-00487-w

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