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Studies on the metabolism and toxicological detection of the new psychoactive designer drug 2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine (25I-NBOMe) in human and rat urine using GC-MS, LC-MSn, and LC-HR-MS/MS

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Abstract

25I-NBOMe, a new psychoactive substance, is a potent 5-HT2A receptor agonist with strong hallucinogenic potential. Recently, it was involved in several fatal and non-fatal intoxication cases. The aim of the present work was to study its phase I and II metabolism and its detectability in urine screening approaches. After application of 25I-NBOMe to male Wistar rats, urine was collected over 24 h. The phase I and II metabolites were identified by LC-HR-MS/MS in urine after suitable workup. For the detectability studies, standard urine screening approaches (SUSA) by GC-MS, LC-MSn, and LC-HR-MS/MS were applied to rat and also to authentic human urine samples submitted for toxicological analysis. Finally, an initial CYP activity screening was performed to identify CYP isoenzymes involved in the major metabolic steps. 25I-NBOMe was mainly metabolized by O-demethylation, O,O-bis-demethylation, hydroxylation, and combinations of these reactions as well as by glucuronidation and sulfation of the main phase I metabolites. All in all, 68 metabolites could be identified. Intake of 25I-NBOMe was detectable mainly via its metabolites by both LC-MS approaches, but not by the GC-MS SUSA. Initial CYP activity screening revealed the involvement of CYP1A2 and CYP3A4 in hydroxylation and CYP2C9 and CYP2C19 in O-demethylation. The presented study demonstrated that 25I-NBOMe was extensively metabolized and could be detected only by the LC-MS screening approaches. Since CYP2C9 and CYP3A4 are involved in initial metabolic steps, drug–drug interactions might occur in certain constellations.

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Acknowledgments

The authors like to thank Julia Dinger, Lilian H. J. Richter, Carsten Schröder, Gabriele Ulrich, Lea Wagmann, Armin A. Weber, Jessica Welter, and Carina S. D. Wink for support and/or helpful discussion.

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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

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

  2. Institute of Forensic Medicine, Forensic Toxicology, Medical Center—University of Freiburg, 79104, Freiburg, Germany

    Volker Auwärter

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

    Simon D. Brandt

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  1. Achim T. Caspar
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  2. Andreas G. Helfer
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Correspondence to Hans H. Maurer.

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Caspar, A.T., Helfer, A.G., Michely, J.A. et al. Studies on the metabolism and toxicological detection of the new psychoactive designer drug 2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine (25I-NBOMe) in human and rat urine using GC-MS, LC-MSn, and LC-HR-MS/MS. Anal Bioanal Chem 407, 6697–6719 (2015). https://doi.org/10.1007/s00216-015-8828-6

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  • DOI: https://doi.org/10.1007/s00216-015-8828-6

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