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

作者: Achim T. Caspar , Andreas G. Helfer , Julian A. Michely , Volker Auwärter , Simon D. Brandt

DOI: 10.1007/S00216-015-8828-6

关键词: UrineCYP1A2Designer drugCYP3A4ChemistrySulfation25I-NBOMeGlucuronidationPharmacologyHydroxylation

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

参考文章(30)
Michael R. Braden, Jason C. Parrish, John C. Naylor, David E. Nichols, Molecular interaction of serotonin 5-HT2A receptor residues Phe339(6.51) and Phe340(6.52) with superpotent N-benzyl phenethylamine agonists. Molecular Pharmacology. ,vol. 70, pp. 1956- 1964 ,(2006) , 10.1124/MOL.106.028720
Martin Hansen, Karina Phonekeo, James S. Paine, Sebastian Leth-Petersen, Mikael Begtrup, Hans Bräuner-Osborne, Jesper L. Kristensen, Synthesis and structure-activity relationships of N-benzyl phenethylamines as 5-HT2A/2C agonists. ACS Chemical Neuroscience. ,vol. 5, pp. 243- 249 ,(2014) , 10.1021/CN400216U
S. Rutherfoord Rose, Justin L. Poklis, Alphonse Poklis, A case of 25I-NBOMe (25-I) intoxication: a new potent 5-HT2A agonist designer drug Clinical Toxicology. ,vol. 51, pp. 174- 177 ,(2013) , 10.3109/15563650.2013.772191
Samuel J. Stellpflug, Samantha E. Kealey, Cullen B. Hegarty, Gregory C. Janis, 2-(4-Iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine (25I-NBOMe): clinical case with unique confirmatory testing. Journal of Medical Toxicology. ,vol. 10, pp. 45- 50 ,(2014) , 10.1007/S13181-013-0314-Y
Carina S. D. Wink, Markus R. Meyer, Tina Braun, Alain Turcant, Hans H. Maurer, Biotransformation and detectability of the designer drug 2,5-dimethoxy-4-propylphenethylamine (2C-P) studied in urine by GC-MS, LC-MS(n), and LC-high-resolution-MS(n). Analytical and Bioanalytical Chemistry. ,vol. 407, pp. 831- 843 ,(2015) , 10.1007/S00216-014-8083-2