Gutenberg Open Science: Chiral pharmacokinetics of tetramisole stereoisomers : enantioselective quantification of levamisole and dexamisole in serum samples from users of adulterated cocaine

Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-8630

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DC Field	Value	Language
dc.contributor.author	Losacker, Moritz	-
dc.contributor.author	Hundertmark, Marica	-
dc.contributor.author	Zörntlein, Siegfried	-
dc.contributor.author	Röhrich, Jörg	-
dc.contributor.author	Hess, Cornelius	-
dc.date.accessioned	2023-01-24T09:27:15Z	-
dc.date.available	2023-01-24T09:27:15Z	-
dc.date.issued	2022	-
dc.identifier.uri	https://openscience.ub.uni-mainz.de/handle/20.500.12030/8646	-
dc.description.abstract	Phenyltetrahydroimidazothiazole (PTHIT, tetramisole) is the most frequently used adulterant of cocaine and exists in the two enantiomeric forms levamsiole (S) and dexamisole (R). Existing studies show diverse fractions of samples containing enantiopure levamsiole, levamisole-enriched mixtures, and racemic tetramisole as adulterant. However, blood samples have never been enantioselectively tested for PTHIT. Because enantiomers are usually metabolized stereoselectively, chiral analysis of blood samples can help estimate the time of drug use, provided that a racemic substance is ingested. Therefore, an enantioselective liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed using a chiral column. Validation of the method was carried out for methanolic substance samples as well as serum samples and showed satisfactory selectivity, sensitivity, linearity (0.05–100 ng/mL), precision, and accuracy; 151 cocaine samples seized in Germany between 2018 and 2021 were analyzed. Most (94%, n = 48) of the 51 PTHIT-positive samples contained racemic tetramsiole, whereas there were two samples containing levamisole-enriched mixtures and one sample containing nearly enantiopure levamisole. Furthermore, 157 cocaine and/or benzoylecgonine-positive forensic serum samples were tested with cocaine-positive samples showing the highest frequency of PTHIT detection (43%). All positive samples contained either dexamisole alone or (R)/(S)-concentration ratios >1 (1.05–70.6). Finally, a self-administration study was conducted with three subjects taking 10 mg of racemic tetramisole each. Although peak concentrations and corresponding times did not differ significantly between the enantiomers, dexamisole showed significantly longer apparent elimination half-lives (7.02–10.0 h) than levamisole (2.87–4.77 h). The resulting steadily increasing (R)/(S)-ratios can therefore be helpful in estimating the time of cocaine consumption.	en_GB
dc.description.sponsorship	Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 491381577	de
dc.language.iso	ger	de
dc.rights	CC BY	*
dc.rights.uri	https://creativecommons.org/licenses/by/4.0/	*
dc.subject.ddc	610 Medizin	de_DE
dc.subject.ddc	610 Medical sciences	en_GB
dc.title	Chiral pharmacokinetics of tetramisole stereoisomers : enantioselective quantification of levamisole and dexamisole in serum samples from users of adulterated cocaine	en_GB
dc.type	Zeitschriftenaufsatz	de
dc.identifier.doi	http://doi.org/10.25358/openscience-8630	-
jgu.type.dinitype	article	en_GB
jgu.type.version	Published version	de
jgu.type.resource	Text	de
jgu.organisation.department	FB 04 Medizin	de
jgu.organisation.number	2700	-
jgu.organisation.name	Johannes Gutenberg-Universität Mainz	-
jgu.rights.accessrights	openAccess	-
jgu.journal.title	Drug testing and analysis	de
jgu.journal.volume	14	de
jgu.journal.issue	6	de
jgu.pages.start	1053	de
jgu.pages.end	1064	de
jgu.publisher.year	2022	-
jgu.publisher.name	Wiley	de
jgu.publisher.place	Hoboken, NJ	de
jgu.publisher.issn	1942-7611	de
jgu.organisation.place	Mainz	-
jgu.subject.ddccode	610	de
jgu.publisher.doi	10.1002/dta.3227	de
jgu.organisation.ror	https://ror.org/023b0x485	-
jgu.subject.dfg	Lebenswissenschaften	de
Appears in collections:	DFG-491381577-H

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