Authors:	Hundertmark, Marica Hess, Cornelius Röhrich, Jörg Wunder, Cora Losacker, Moritz
Title:	Analysis of tetramisole metabolites : is “Aminorex” found in forensic samples of cocaine users actually 4-phenyl-2-imidazolidinone?
Online publication date:	12-Sep-2023
Year of first publication:	2023
Language:	english
Abstract:	Phenyltetrahydroimidazothiazole (PTHIT, tetramisole) is a common adulterant in cocaine samples. Little is known about its human metabolism. p-hydroxy-PTHIT has long been the only proven phase-I-metabolite. Another putative metabolite is the stimulant aminorex. However, data on its analytical proof is rare and contradictory. Even less known is its constitutional isomer 4-phenyl-2-imidazolidinone which has only been proven in animal samples so far. The aim of the study was to get insight into the metabolism of PTHIT after controlled nasal uptake of PTHIT and in real forensic cocaine/benzoylecgonine-positive samples. A liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was validated for quantification of 4-phenyl-2-imidazolidinone and p-hydroxy-PTHIT (LOQ 0.05 ng/ml each). Selectivity was ensured for 4-phenyl-2-imidazolidinone and aminorex (LOD 0.05 ng/ml). After controlled nasal uptake of tetramisole (10 mg, n = 3) a shorter half-life for p-hydroxy-PTHIT (3.4–5.8 h) was determined than for 4-phenyl-2-imidazolidinone (14.0–15.9 h). p-hydroxy-PTHIT (33%) and 4-phenyl-2-imidazolidinone (51%) were also detected in serum samples from cocaine users tested previously positive for PTHIT (n = 73). Aminorex was never detected. The potential of misinterpreting 4-phenyl-2-imidazolidinone as aminorex was tested using a gas chromatography–mass spectrometry (GC–MS) method used in the literature and an in-house liquid chromatography-time-of-flight mass spectrometry (LC-QTOF) screening-method. Using GC–MS the analysed bis-trimethylsilyl-derivatives cannot be differentiated due to co-elution. Both substances were chromatographically separated using the LC-QTOF method, but library comparison workflows misinterpreted 4-phenyl-2-imidazolidinone as aminorex. It seems likely that aminorex, which was allegedly identified as a metabolite of PTHIT in samples of cocaine users in previous studies, is in fact 4-phenyl-2-imidazolidinone.
DDC:	610 Medizin 610 Medical sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 04 Medizin
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-9535
Version:	Published version
Publication type:	Zeitschriftenaufsatz
License:	CC BY
Information on rights of use:	https://creativecommons.org/licenses/by/4.0/
Journal:	Drug testing and analysis 15 8
Pages or article number:	865 878
Publisher:	Wiley
Publisher place:	Hoboken, NJ
Issue date:	2023
ISSN:	1942-7611
Publisher DOI:	10.1002/dta.3482
Appears in collections:	DFG-491381577-H