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Benzofuran analogues of amphetamine and methamphetamine: studies on the metabolism and toxicological analysis of 5-APB and 5-MAPB in urine and plasma using GC-MS and LC-(HR)-MSn techniques

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Abstract

5-APB (5-(2-aminopropyl)benzofuran) and its N-methyl derivative 5-MAPB (N-methyl-5-(2-aminopropyl)benzofuran) are analogues of amphetamine and methamphetamine, respectively, and belong to the so-called novel psychoactive substances (NPS). They were consumed as stimulants or entactogens with euphoric and empathogenic effects. Being controlled in some countries, both compounds should be covered by drug testing in clinical and forensic toxicology. Therefore, metabolism studies have been performed by working up rat urine samples after a high single dose of the corresponding NPS with solid-phase extraction without and after enzymatic conjugates cleavage. The phase I metabolites were separated and identified after acetylation by GC-MS and/or LC-HR-MSn and the phase II metabolites by LC-HR-MSn. The main metabolite of 5-APB was 3-carboxymethyl-4-hydroxy amphetamine and the main metabolites of 5-MAPB were 5-APB (N-demethyl metabolite) and 3-carboxymethyl-4-hydroxy methamphetamine. The cytochrome P450 (CYP) isoenzymes involved in the 5-MAPB N-demethylation were CYP1A2, CYP2B6, CYP2C19, and CYP2D6, and according to the kinetic parameters, CYP2B6 was responsible for the main part of the total CYP-dependent clearance. An intake of a common users’ dose of 5-APB or 5-MAPB could be confirmed in rat urine using the authors’ GC-MS and the LC-MSn standard urine screening approaches with the corresponding parent drugs as major target. In authentic human urine samples after ingestion of unknown doses of 5-MAPB, both metabolites could also be detected besides the parent drug. The plasma concentrations determined in six clinical cases ranged from 5 to 124 μg/L for 5-MAPB and from 1 to 38 μg/L for its N-demethyl metabolite 5-APB.

Contribution of the given CYPs to the 5-MAPB N-demethylation

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Acknowledgments

The authors like to thank Achim Caspar, Julia Dinger, Andreas Helfer, Julian Michely, Carina Wink, Gabriele Ulrich, Carsten Schröder, and Armin A. Weber for support and/or helpful discussion.

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Authors and Affiliations

  1. Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Saarland University, 66421, Homburg, Saar, Germany

    Jessica Welter, Markus R. Meyer & Hans H. Maurer

  2. Department of Pharmacology and Therapeutics, Trinity Centre for Health and Sciences, St. James’s Hospital, Dublin 8, Ireland

    Pierce Kavanagh

Authors
  1. Jessica Welter
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  2. Pierce Kavanagh
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  3. Markus R. Meyer
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  4. Hans H. Maurer
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Correspondence to Hans H. Maurer.

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Welter, J., Kavanagh, P., Meyer, M.R. et al. Benzofuran analogues of amphetamine and methamphetamine: studies on the metabolism and toxicological analysis of 5-APB and 5-MAPB in urine and plasma using GC-MS and LC-(HR)-MSn techniques. Anal Bioanal Chem 407, 1371–1388 (2015). https://doi.org/10.1007/s00216-014-8360-0

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  • DOI: https://doi.org/10.1007/s00216-014-8360-0

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