2C-B-Fly-NBOMe Metabolites in Rat Urine, Human Liver Microsomes and <i>C. elegans</i>: Confirmation with Synthesized Analytical Standards
Compounds from the <i>N</i>-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 th...
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oai:doaj.org-article:59fea8e87707439d924324836461c76c2021-11-25T18:20:50Z2C-B-Fly-NBOMe Metabolites in Rat Urine, Human Liver Microsomes and <i>C. elegans</i>: Confirmation with Synthesized Analytical Standards10.3390/metabo111107752218-1989https://doaj.org/article/59fea8e87707439d924324836461c76c2021-11-01T00:00:00Zhttps://www.mdpi.com/2218-1989/11/11/775https://doaj.org/toc/2218-1989Compounds from the <i>N</i>-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)-<i>N</i>-(2-methoxybenzyl)ethan-1-amine (2C-B-Fly-NBOMe) in three different systems: isolated human liver microsomes, <i>Cunninghamella elegans</i> 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, <i>O</i>-demethylation, oxidative debromination, and to a lesser extent also <i>N</i>-demethoxybenzylation, followed by glucuronidation and/or <i>N</i>-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, <i>N</i>-oxygenated, and dibrominated metabolites.Jitka NykodemováAnna ŠulákováPetr PalivecHedvika ČeškováSilvie RimpelováKlára ŠíchováTereza LeonhardtBronislav JurásekKateřina HájkováTomáš PáleníčekMartin KuchařMDPI AGarticle2C-B-Fly-NBOMeLC–MSmetabolite synthesismetabolomicshuman liver microsomes<i>Cunninghamella elegans</i>MicrobiologyQR1-502ENMetabolites, Vol 11, Iss 775, p 775 (2021) |
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DOAJ |
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| topic |
2C-B-Fly-NBOMe LC–MS metabolite synthesis metabolomics human liver microsomes <i>Cunninghamella elegans</i> Microbiology QR1-502 |
| spellingShingle |
2C-B-Fly-NBOMe LC–MS metabolite synthesis metabolomics human liver microsomes <i>Cunninghamella elegans</i> Microbiology QR1-502 Jitka Nykodemová Anna Šuláková Petr Palivec Hedvika Češková Silvie Rimpelová Klára Šíchová Tereza Leonhardt Bronislav Jurásek Kateřina Hájková Tomáš Páleníček Martin Kuchař 2C-B-Fly-NBOMe Metabolites in Rat Urine, Human Liver Microsomes and <i>C. elegans</i>: Confirmation with Synthesized Analytical Standards |
| description |
Compounds from the <i>N</i>-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)-<i>N</i>-(2-methoxybenzyl)ethan-1-amine (2C-B-Fly-NBOMe) in three different systems: isolated human liver microsomes, <i>Cunninghamella elegans</i> 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, <i>O</i>-demethylation, oxidative debromination, and to a lesser extent also <i>N</i>-demethoxybenzylation, followed by glucuronidation and/or <i>N</i>-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, <i>N</i>-oxygenated, and dibrominated metabolites. |
| format |
article |
| author |
Jitka Nykodemová Anna Šuláková Petr Palivec Hedvika Češková Silvie Rimpelová Klára Šíchová Tereza Leonhardt Bronislav Jurásek Kateřina Hájková Tomáš Páleníček Martin Kuchař |
| author_facet |
Jitka Nykodemová Anna Šuláková Petr Palivec Hedvika Češková Silvie Rimpelová Klára Šíchová Tereza Leonhardt Bronislav Jurásek Kateřina Hájková Tomáš Páleníček Martin Kuchař |
| author_sort |
Jitka Nykodemová |
| title |
2C-B-Fly-NBOMe Metabolites in Rat Urine, Human Liver Microsomes and <i>C. elegans</i>: Confirmation with Synthesized Analytical Standards |
| title_short |
2C-B-Fly-NBOMe Metabolites in Rat Urine, Human Liver Microsomes and <i>C. elegans</i>: Confirmation with Synthesized Analytical Standards |
| title_full |
2C-B-Fly-NBOMe Metabolites in Rat Urine, Human Liver Microsomes and <i>C. elegans</i>: Confirmation with Synthesized Analytical Standards |
| title_fullStr |
2C-B-Fly-NBOMe Metabolites in Rat Urine, Human Liver Microsomes and <i>C. elegans</i>: Confirmation with Synthesized Analytical Standards |
| title_full_unstemmed |
2C-B-Fly-NBOMe Metabolites in Rat Urine, Human Liver Microsomes and <i>C. elegans</i>: Confirmation with Synthesized Analytical Standards |
| title_sort |
2c-b-fly-nbome metabolites in rat urine, human liver microsomes and <i>c. elegans</i>: confirmation with synthesized analytical standards |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/59fea8e87707439d924324836461c76c |
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