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Metabolism of the new psychoactive substances N,N-diallyltryptamine (DALT) and 5-methoxy-DALT and their detectability in urine by GC–MS, LC–MSn, and LC–HR–MS–MS

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Abstract

N,N-Diallyltryptamine (DALT) and 5-methoxy-DALT (5-MeO-DALT) are synthetic tryptamine derivatives commonly referred to as so-called new psychoactive substances (NPS). They have psychoactive effects that may be similar to those of other tryptamine derivatives. The objectives of this work were to study the metabolic fate and detectability, in urine, of DALT and 5-MeO-DALT. For metabolism studies, rat urine obtained after high-dose administration was prepared by precipitation and analyzed by liquid chromatography–high-resolution mass spectrometry (LC–HR–MS–MS). On the basis of the metabolites identified, several aromatic and aliphatic hydroxylations, N-dealkylation, N-oxidation, and combinations thereof are proposed as the main metabolic pathways for both compounds. O-Demethylation of 5-MeO-DALT was also observed, in addition to extensive glucuronidation or sulfation of both compounds after phase I transformation. The cytochrome P450 (CYP) isoenzymes predominantly involved in DALT metabolism were CYP2C19, CYP2D6, and CYP3A4; those mainly involved in 5-MeO-DALT metabolism were CYP1A2, CYP2C19, CYP2D6, and CYP3A4. For detectability studies, rat urine was screened by GC–MS, LC–MSn, and LC–HR–MS–MS after administration of low doses. LC–MSn and LC–HR–MS–MS were deemed suitable for monitoring consumption of both compounds. The most abundant targets were a ring hydroxy metabolite of DALT, the N,O-bis-dealkyl metabolite of 5-MeO-DALT, and their glucuronides. GC–MS enabled screening of DALT by use of its main metabolites only.

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Acknowledgments

The authors thank Achim T. Caspar, Julia Dinger, Golo M. J. Meyer, Jessica Welter, Carina S. D. Wink, Carsten Schröder, Gabriele Ulrich, and Armin A. Weber for their support and/or helpful discussion.

Conflict of interest

The authors declare there are no conflicts of interest.

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Author notes

  1. Markus R. Meyer

    Present address: Farmakologiska laboratoriet, Klinisk farmakologi, Karolinska Universitetssjukhuset Huddinge, Karolinska Institutet, 141 86, Stockholm, Sweden

Authors and Affiliations

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

    Julian A. Michely, Andreas G. Helfer, Markus R. Meyer & Hans H. Maurer

  2. School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, L3 3AF, Liverpool, UK

    Simon D. Brandt

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Correspondence to Hans H. Maurer.

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Michely, J.A., Helfer, A.G., Brandt, S.D. et al. Metabolism of the new psychoactive substances N,N-diallyltryptamine (DALT) and 5-methoxy-DALT and their detectability in urine by GC–MS, LC–MSn, and LC–HR–MS–MS. Anal Bioanal Chem 407, 7831–7842 (2015). https://doi.org/10.1007/s00216-015-8955-0

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