In Vitro Metabolism of 25B-NBF, 2-(4-Bromo-2,5-Dimethoxyphenyl)-<i>N</i>-(2-Fluorobenzyl)ethanamine, in Human Hepatocytes Using Liquid Chromatography–Mass Spectrometry
25B-NBF, 2-(4-bromo-2,5-dimethoxyphenyl)-<i>N</i>-(2-fluorobenzyl)ethanamine, is a new psychoactive substance classified as a phenethylamine. It is a potent agonist of the 5-hydroxytryptamine receptor, but little is known about its metabolism and elimination properties since it was disco...
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MDPI AG
2019-02-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/24/4/818 |
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| author | Ju-Hyun Kim Sunjoo Kim Jaesin Lee Sangwhan In Yong-Yeon Cho Han Chang Kang Joo Young Lee Hye Suk Lee |
| author_facet | Ju-Hyun Kim Sunjoo Kim Jaesin Lee Sangwhan In Yong-Yeon Cho Han Chang Kang Joo Young Lee Hye Suk Lee |
| author_sort | Ju-Hyun Kim |
| collection | DOAJ |
| description | 25B-NBF, 2-(4-bromo-2,5-dimethoxyphenyl)-<i>N</i>-(2-fluorobenzyl)ethanamine, is a new psychoactive substance classified as a phenethylamine. It is a potent agonist of the 5-hydroxytryptamine receptor, but little is known about its metabolism and elimination properties since it was discovered. To aid 25B-NBF abuse screening, the metabolic characteristics of 25B-NBF were investigated in human hepatocytes and human cDNA-expressed cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) enzymes using liquid chromatography⁻high resolution mass spectrometry. At a hepatic extraction ratio of 0.80, 25B-NBF was extensively metabolized into 33 metabolites via hydroxylation, <i>O</i>-demethylation, bis-<i>O</i>-demethylation, <i>N</i>-debenzylation, glucuronidation, sulfation, and acetylation after incubation with pooled human hepatocytes. The metabolism of 25B-NBF was catalyzed by CYP1A1, CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2J2, CYP3A4, and UGT2B7 enzymes. Based on these results, it is necessary to develop a bioanalytical method for the determination of not only 25B-NBF but also its metabolites in biological samples for the screening of 25B-NBF abuse. |
| first_indexed | 2024-04-13T09:51:53Z |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-13T09:51:53Z |
| publishDate | 2019-02-01 |
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| series | Molecules |
| spelling | doaj.art-5dbc3b48b9b4422986e9ba1194bc6a682022-12-22T02:51:34ZengMDPI AGMolecules1420-30492019-02-0124481810.3390/molecules24040818molecules24040818In Vitro Metabolism of 25B-NBF, 2-(4-Bromo-2,5-Dimethoxyphenyl)-<i>N</i>-(2-Fluorobenzyl)ethanamine, in Human Hepatocytes Using Liquid Chromatography–Mass SpectrometryJu-Hyun Kim0Sunjoo Kim1Jaesin Lee2Sangwhan In3Yong-Yeon Cho4Han Chang Kang5Joo Young Lee6Hye Suk Lee7BK21 PLUS Team for Creative Leader Program for Pharmacomics-based Future Pharmacy, College of Pharmacy, The Catholic University of Korea, Bucheon 14662, KoreaBK21 PLUS Team for Creative Leader Program for Pharmacomics-based Future Pharmacy, College of Pharmacy, The Catholic University of Korea, Bucheon 14662, KoreaNational Forensic Service, Wonju 24460, KoreaNational Forensic Service, Wonju 24460, KoreaBK21 PLUS Team for Creative Leader Program for Pharmacomics-based Future Pharmacy, College of Pharmacy, The Catholic University of Korea, Bucheon 14662, KoreaBK21 PLUS Team for Creative Leader Program for Pharmacomics-based Future Pharmacy, College of Pharmacy, The Catholic University of Korea, Bucheon 14662, KoreaBK21 PLUS Team for Creative Leader Program for Pharmacomics-based Future Pharmacy, College of Pharmacy, The Catholic University of Korea, Bucheon 14662, KoreaBK21 PLUS Team for Creative Leader Program for Pharmacomics-based Future Pharmacy, College of Pharmacy, The Catholic University of Korea, Bucheon 14662, Korea25B-NBF, 2-(4-bromo-2,5-dimethoxyphenyl)-<i>N</i>-(2-fluorobenzyl)ethanamine, is a new psychoactive substance classified as a phenethylamine. It is a potent agonist of the 5-hydroxytryptamine receptor, but little is known about its metabolism and elimination properties since it was discovered. To aid 25B-NBF abuse screening, the metabolic characteristics of 25B-NBF were investigated in human hepatocytes and human cDNA-expressed cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) enzymes using liquid chromatography⁻high resolution mass spectrometry. At a hepatic extraction ratio of 0.80, 25B-NBF was extensively metabolized into 33 metabolites via hydroxylation, <i>O</i>-demethylation, bis-<i>O</i>-demethylation, <i>N</i>-debenzylation, glucuronidation, sulfation, and acetylation after incubation with pooled human hepatocytes. The metabolism of 25B-NBF was catalyzed by CYP1A1, CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2J2, CYP3A4, and UGT2B7 enzymes. Based on these results, it is necessary to develop a bioanalytical method for the determination of not only 25B-NBF but also its metabolites in biological samples for the screening of 25B-NBF abuse.https://www.mdpi.com/1420-3049/24/4/81825B-NBF metabolismliquid chromatography-high resolution mass spectrometryhuman hepatocyteCYPUGT |
| spellingShingle | Ju-Hyun Kim Sunjoo Kim Jaesin Lee Sangwhan In Yong-Yeon Cho Han Chang Kang Joo Young Lee Hye Suk Lee In Vitro Metabolism of 25B-NBF, 2-(4-Bromo-2,5-Dimethoxyphenyl)-<i>N</i>-(2-Fluorobenzyl)ethanamine, in Human Hepatocytes Using Liquid Chromatography–Mass Spectrometry Molecules 25B-NBF metabolism liquid chromatography-high resolution mass spectrometry human hepatocyte CYP UGT |
| title | In Vitro Metabolism of 25B-NBF, 2-(4-Bromo-2,5-Dimethoxyphenyl)-<i>N</i>-(2-Fluorobenzyl)ethanamine, in Human Hepatocytes Using Liquid Chromatography–Mass Spectrometry |
| title_full | In Vitro Metabolism of 25B-NBF, 2-(4-Bromo-2,5-Dimethoxyphenyl)-<i>N</i>-(2-Fluorobenzyl)ethanamine, in Human Hepatocytes Using Liquid Chromatography–Mass Spectrometry |
| title_fullStr | In Vitro Metabolism of 25B-NBF, 2-(4-Bromo-2,5-Dimethoxyphenyl)-<i>N</i>-(2-Fluorobenzyl)ethanamine, in Human Hepatocytes Using Liquid Chromatography–Mass Spectrometry |
| title_full_unstemmed | In Vitro Metabolism of 25B-NBF, 2-(4-Bromo-2,5-Dimethoxyphenyl)-<i>N</i>-(2-Fluorobenzyl)ethanamine, in Human Hepatocytes Using Liquid Chromatography–Mass Spectrometry |
| title_short | In Vitro Metabolism of 25B-NBF, 2-(4-Bromo-2,5-Dimethoxyphenyl)-<i>N</i>-(2-Fluorobenzyl)ethanamine, in Human Hepatocytes Using Liquid Chromatography–Mass Spectrometry |
| title_sort | in vitro metabolism of 25b nbf 2 4 bromo 2 5 dimethoxyphenyl i n i 2 fluorobenzyl ethanamine in human hepatocytes using liquid chromatography mass spectrometry |
| topic | 25B-NBF metabolism liquid chromatography-high resolution mass spectrometry human hepatocyte CYP UGT |
| url | https://www.mdpi.com/1420-3049/24/4/818 |
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