Title
Liquid chromatography-quadrupole time-of-flight mass spectrometry for screening in vitro drug metabolites in humans : investigation on seven phenethylamine-based designer drugsLiquid chromatography-quadrupole time-of-flight mass spectrometry for screening in vitro drug metabolites in humans : investigation on seven phenethylamine-based designer drugs
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences. Pharmacy
Research group
Toxicological Centre
Publication type
article
Publication
Oxford,
Subject
Chemistry
Pharmacology. Therapy
Source (journal)
Journal of pharmaceutical and biomedical analysis. - Oxford
Volume/pages
114(2015), p. 355-375
ISSN
0731-7085
ISI
000360780700049
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Phenethylamine-based designer drugs are prevalent within the new psychoactive substance market. Characterisation of their metabolites is important in order to identify suitable biomarkers which can be used for better monitoring their consumption. Careful design of in vitro metabolism experiments using subcellular liver fractions will assist in obtaining reliable outcomes for such purposes. The objective of this study was to stepwise investigate the in vitro human metabolism of seven phenethylamine-based designer drugs using individual families of enzymes. This included para-methoxyamphetamine, para-methoxymethamphetamine, 4-methylthioamphetamine, N-methyl-benzodioxolylbutanamine, benzodioxolylbutanamine, 5-(2-aminopropyl) benzofuran and 6(2-aminopropyl) benzofuran. Identification and structural elucidation of the metabolites was performed using liquid chromatography-quadrupole-time-of-flight mass spectrometry. The targeted drugs were mainly metabolised by cytochrome P450 enzymes via O-dealkylation as the major pathway, followed by N-dealkylation, oxidation of unsubstituted C atoms and deamination (to a small extent). These drugs were largely free from Phase II metabolism. Only a limited number of metabolites were found which was consistent with the existing literature for other phenethylamine-based drugs. Also, the metabolism of most of the targeted drugs progressed at slow rate. The reproducibility of the identified metabolites was assessed through examining formation patterns using different incubation times, substrate and enzyme concentrations. Completion of the work has led to a set of metabolites which are representative for specific detection of these drugs in intoxicated individuals and also for meaningful evaluation of their use in communities by wastewater-based drug epidemiology. (C) 2015 Elsevier B.V. All rights reserved.
E-info
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https://repository.uantwerpen.be/docman/iruaauth/b37a0f/127822.pdf
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Full text (open access)
https://repository.uantwerpen.be/docman/irua/766eff/127822_2016_10_10.pdf
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