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2C-B-Fly-NBOMe Metabolites in Rat Urine, Human Liver Microsomes and C. elegans: Confirmation with Synthesized Analytical Standards

Compounds from the N-benzylphenethylamine (NBPEA) class of novel psychoactive substances are being increasingly utilized in neurobiological and clinical research, as diagnostic tools, or for recreational purposes. To understand the pharmacology, safety, or potential toxicity of these substances, elu...

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Autores principales: Nykodemová, Jitka, Šuláková, Anna, Palivec, Petr, Češková, Hedvika, Rimpelová, Silvie, Šíchová, Klára, Leonhardt, Tereza, Jurásek, Bronislav, Hájková, Kateřina, Páleníček, Tomáš, Kuchař, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8624686/
https://www.ncbi.nlm.nih.gov/pubmed/34822433
http://dx.doi.org/10.3390/metabo11110775
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author Nykodemová, Jitka
Šuláková, Anna
Palivec, Petr
Češková, Hedvika
Rimpelová, Silvie
Šíchová, Klára
Leonhardt, Tereza
Jurásek, Bronislav
Hájková, Kateřina
Páleníček, Tomáš
Kuchař, Martin
author_facet Nykodemová, Jitka
Šuláková, Anna
Palivec, Petr
Češková, Hedvika
Rimpelová, Silvie
Šíchová, Klára
Leonhardt, Tereza
Jurásek, Bronislav
Hájková, Kateřina
Páleníček, Tomáš
Kuchař, Martin
author_sort Nykodemová, Jitka
collection PubMed
description Compounds from the N-benzylphenethylamine (NBPEA) class of novel psychoactive substances are being increasingly utilized in neurobiological and clinical research, as diagnostic tools, or for recreational purposes. To understand the pharmacology, safety, or potential toxicity of these substances, elucidating their metabolic fate is therefore of the utmost interest. Several studies on NBPEA metabolism have emerged, but scarce information about substances with a tetrahydrobenzodifuran (“Fly”) moiety is available. Here, we investigated the metabolism of 2-(8-bromo-2,3,6,7-tetrahydrobenzo[1,2-b:4,5-b’]difuran-4-yl)-N-(2-methoxybenzyl)ethan-1-amine (2C-B-Fly-NBOMe) in three different systems: isolated human liver microsomes, Cunninghamella elegans mycelium, and in rats in vivo. Phase I and II metabolites of 2C-B-Fly-NBOMe were first detected in an untargeted screening and identified by liquid chromatography–tandem mass spectrometry (LC–MS/MS). Several hypothesized metabolites were then synthesized as reference standards; knowledge of their fragmentation patterns was utilized for confirmation or tentative identification of isomers. Altogether, thirty-five phase I and nine phase II 2C-B-Fly-NBOMe metabolites were detected. Major detected metabolic pathways were mono- and poly-hydroxylation, O-demethylation, oxidative debromination, and to a lesser extent also N-demethoxybenzylation, followed by glucuronidation and/or N-acetylation. Differences were observed for the three used media. The highest number of metabolites and at highest concentration were found in human liver microsomes. In vivo metabolites detected from rat urine included two poly-hydroxylated metabolites found only in this media. Mycelium matrix contained several dehydrogenated, N-oxygenated, and dibrominated metabolites.
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spelling pubmed-86246862021-11-27 2C-B-Fly-NBOMe Metabolites in Rat Urine, Human Liver Microsomes and C. elegans: Confirmation with Synthesized Analytical Standards Nykodemová, Jitka Šuláková, Anna Palivec, Petr Češková, Hedvika Rimpelová, Silvie Šíchová, Klára Leonhardt, Tereza Jurásek, Bronislav Hájková, Kateřina Páleníček, Tomáš Kuchař, Martin Metabolites Article Compounds from the N-benzylphenethylamine (NBPEA) class of novel psychoactive substances are being increasingly utilized in neurobiological and clinical research, as diagnostic tools, or for recreational purposes. To understand the pharmacology, safety, or potential toxicity of these substances, elucidating their metabolic fate is therefore of the utmost interest. Several studies on NBPEA metabolism have emerged, but scarce information about substances with a tetrahydrobenzodifuran (“Fly”) moiety is available. Here, we investigated the metabolism of 2-(8-bromo-2,3,6,7-tetrahydrobenzo[1,2-b:4,5-b’]difuran-4-yl)-N-(2-methoxybenzyl)ethan-1-amine (2C-B-Fly-NBOMe) in three different systems: isolated human liver microsomes, Cunninghamella elegans mycelium, and in rats in vivo. Phase I and II metabolites of 2C-B-Fly-NBOMe were first detected in an untargeted screening and identified by liquid chromatography–tandem mass spectrometry (LC–MS/MS). Several hypothesized metabolites were then synthesized as reference standards; knowledge of their fragmentation patterns was utilized for confirmation or tentative identification of isomers. Altogether, thirty-five phase I and nine phase II 2C-B-Fly-NBOMe metabolites were detected. Major detected metabolic pathways were mono- and poly-hydroxylation, O-demethylation, oxidative debromination, and to a lesser extent also N-demethoxybenzylation, followed by glucuronidation and/or N-acetylation. Differences were observed for the three used media. The highest number of metabolites and at highest concentration were found in human liver microsomes. In vivo metabolites detected from rat urine included two poly-hydroxylated metabolites found only in this media. Mycelium matrix contained several dehydrogenated, N-oxygenated, and dibrominated metabolites. MDPI 2021-11-12 /pmc/articles/PMC8624686/ /pubmed/34822433 http://dx.doi.org/10.3390/metabo11110775 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nykodemová, Jitka
Šuláková, Anna
Palivec, Petr
Češková, Hedvika
Rimpelová, Silvie
Šíchová, Klára
Leonhardt, Tereza
Jurásek, Bronislav
Hájková, Kateřina
Páleníček, Tomáš
Kuchař, Martin
2C-B-Fly-NBOMe Metabolites in Rat Urine, Human Liver Microsomes and C. elegans: Confirmation with Synthesized Analytical Standards
title 2C-B-Fly-NBOMe Metabolites in Rat Urine, Human Liver Microsomes and C. elegans: Confirmation with Synthesized Analytical Standards
title_full 2C-B-Fly-NBOMe Metabolites in Rat Urine, Human Liver Microsomes and C. elegans: Confirmation with Synthesized Analytical Standards
title_fullStr 2C-B-Fly-NBOMe Metabolites in Rat Urine, Human Liver Microsomes and C. elegans: Confirmation with Synthesized Analytical Standards
title_full_unstemmed 2C-B-Fly-NBOMe Metabolites in Rat Urine, Human Liver Microsomes and C. elegans: Confirmation with Synthesized Analytical Standards
title_short 2C-B-Fly-NBOMe Metabolites in Rat Urine, Human Liver Microsomes and C. elegans: Confirmation with Synthesized Analytical Standards
title_sort 2c-b-fly-nbome metabolites in rat urine, human liver microsomes and c. elegans: confirmation with synthesized analytical standards
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8624686/
https://www.ncbi.nlm.nih.gov/pubmed/34822433
http://dx.doi.org/10.3390/metabo11110775
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