期刊
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
卷 114, 期 -, 页码 355-375出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jpba.2015.06.016
关键词
New psychoactive substances; Metabolite characterisation; High-resolution mass spectrometry; Wastewater-based epidemiology; LC-QTOF-MS analysis
资金
- UQ Collaboration and Industry Engagement Fund (UQCIEF) [608290]
- Collaborative Research Seeding Grants of the Faculty of Health and Behavioural Sciences (UQHABS) [608670]
- FWO Flanders
- European Union [295138, 316665, 317205]
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.
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