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Metabolic fate, mass spectral fragmentation, detectability, and differentiation in urine of the benzofuran designer drugs 6-APB and 6-MAPB in comparison to their 5-isomers using GC-MS and LC-(HR)-MSn techniques

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Abstract

The number of so-called new psychoactive substances (NPS) is still increasing by modification of the chemical structure of known (scheduled) drugs. As analogues of amphetamines, 2-aminopropyl-benzofurans were sold. They were consumed because of their euphoric and empathogenic effects. After the 5-(2-aminopropyl)benzofurans, the 6-(2-aminopropyl)benzofuran isomers appeared. Thus, the question arose whether the metabolic fate, the mass spectral fragmentation, and the detectability in urine are comparable or different and how an intake can be differentiated. In the present study, 6-(2-aminopropyl)benzofuran (6-APB) and its N-methyl derivative 6-MAPB (N-methyl-6-(2-aminopropyl)benzofuran) were investigated to answer these questions. The metabolites of both drugs were identified in rat urine and human liver preparations using GC-MS and/or liquid chromatography-high resolution-mass spectrometry (LC-HR-MSn). Besides the parent drug, the main metabolite of 6-APB was 4-carboxymethyl-3-hydroxy amphetamine and the main metabolites of 6-MAPB were 6-APB (N-demethyl metabolite) and 4-carboxymethyl-3-hydroxy methamphetamine. The cytochrome P450 (CYP) isoenzymes involved in the 6-MAPB N-demethylation were CYP1A2, CYP2D6, and CYP3A4. An intake of a common users’ dose of 6-APB or 6-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 allowing their differentiation. Furthermore, a differentiation of 6-APB and 6-MAPB in urine from their positional isomers 5-APB and 5-MAPB was successfully performed after solid phase extraction and heptafluorobutyrylation by GC-MS via their retention times.

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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 the 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. School of Pharmacy & Biomolecular Sciences, Liverpool John Moores University, James Parsons Building, Byrom Street, Liverpool, L3 3AF, UK

    Simon D. Brandt

  3. 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. Simon D. Brandt
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  3. Pierce Kavanagh
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  4. Markus R. Meyer
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  5. Hans H. Maurer
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Correspondence to Hans H. Maurer.

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Welter, J., Brandt, S.D., Kavanagh, P. et al. Metabolic fate, mass spectral fragmentation, detectability, and differentiation in urine of the benzofuran designer drugs 6-APB and 6-MAPB in comparison to their 5-isomers using GC-MS and LC-(HR)-MSn techniques. Anal Bioanal Chem 407, 3457–3470 (2015). https://doi.org/10.1007/s00216-015-8552-2

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