Identification of In Vivo Metabolites of Dictamnine in Mice Using HPLC-LTQ-Orbitrap Mass Spectrometry
Dictamnine (4-methoxyfuro[2,3-b]quinolone, DIC), a common furoquinoline alkaloid in the family of Rutaceae, showed diverse biological activities. To investigate the in vivo metabolic pathways of DIC, metabolism of DIC in mice was studied using a high-performance liquid chromatography coupled to elec...
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| Format: | Article |
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Wiley
2018-01-01
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| Series: | Journal of Analytical Methods in Chemistry |
| Online Access: | http://dx.doi.org/10.1155/2018/3567647 |
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| author | Yudong Fu Yujie Deng Qing Yu Xuxia Meng Dabo Wang Pei Wang Ping Wang |
| author_facet | Yudong Fu Yujie Deng Qing Yu Xuxia Meng Dabo Wang Pei Wang Ping Wang |
| author_sort | Yudong Fu |
| collection | DOAJ |
| description | Dictamnine (4-methoxyfuro[2,3-b]quinolone, DIC), a common furoquinoline alkaloid in the family of Rutaceae, showed diverse biological activities. To investigate the in vivo metabolic pathways of DIC, metabolism of DIC in mice was studied using a high-performance liquid chromatography coupled to electrospray ionization of hybrid linear trap quadrupole orbitrap (HPLC-LTQ-Orbitrap) mass spectrometer. Nine metabolites were identified in the DIC-treated mouse urine, plasma, and fecal samples, of which two were identified as new metabolites. The major metabolic pathways of DIC in animal and human liver microsomes were confirmed in the present study, including o-demethylation, monohydroxylation, N-oxidation, and 2,3-olefinic epoxidation pathways. For the first time, a mono-acetylcysteine conjugate of DIC (M9) was detected from DIC-treated mouse urine and plasma samples, and 4-methoxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid (M10) and 2-(2,8-dihydroxy-4-methoxyquinolin-3-yl)acetaldehyde (M11) were identified as new metabolites of DIC; furthermore, using an in vitro human fecal incubation model, furo[2,3-b]quinolin-4-ol (M1) was verified to be a microbial demethylated metabolite of DIC. Collectively, the present study provided new information on the in vivo metabolic fate of DIC. |
| format | Article |
| id | doaj-art-8bbcd615e56e4f0b87929051fbb78a2c |
| institution | Kabale University |
| issn | 2090-8865 2090-8873 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
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| series | Journal of Analytical Methods in Chemistry |
| spelling | doaj-art-8bbcd615e56e4f0b87929051fbb78a2c2025-02-03T05:50:51ZengWileyJournal of Analytical Methods in Chemistry2090-88652090-88732018-01-01201810.1155/2018/35676473567647Identification of In Vivo Metabolites of Dictamnine in Mice Using HPLC-LTQ-Orbitrap Mass SpectrometryYudong Fu0Yujie Deng1Qing Yu2Xuxia Meng3Dabo Wang4Pei Wang5Ping Wang6Department of Endocrinology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao 266071, ChinaDepartment of Ophthalmology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao 266071, ChinaDepartment of Ophthalmology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao 266071, ChinaDepartment of Endocrinology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao 266071, ChinaDepartment of Endocrinology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao 266071, ChinaSchool of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, ChinaDepartment of Ophthalmology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao 266071, ChinaDictamnine (4-methoxyfuro[2,3-b]quinolone, DIC), a common furoquinoline alkaloid in the family of Rutaceae, showed diverse biological activities. To investigate the in vivo metabolic pathways of DIC, metabolism of DIC in mice was studied using a high-performance liquid chromatography coupled to electrospray ionization of hybrid linear trap quadrupole orbitrap (HPLC-LTQ-Orbitrap) mass spectrometer. Nine metabolites were identified in the DIC-treated mouse urine, plasma, and fecal samples, of which two were identified as new metabolites. The major metabolic pathways of DIC in animal and human liver microsomes were confirmed in the present study, including o-demethylation, monohydroxylation, N-oxidation, and 2,3-olefinic epoxidation pathways. For the first time, a mono-acetylcysteine conjugate of DIC (M9) was detected from DIC-treated mouse urine and plasma samples, and 4-methoxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid (M10) and 2-(2,8-dihydroxy-4-methoxyquinolin-3-yl)acetaldehyde (M11) were identified as new metabolites of DIC; furthermore, using an in vitro human fecal incubation model, furo[2,3-b]quinolin-4-ol (M1) was verified to be a microbial demethylated metabolite of DIC. Collectively, the present study provided new information on the in vivo metabolic fate of DIC.http://dx.doi.org/10.1155/2018/3567647 |
| spellingShingle | Yudong Fu Yujie Deng Qing Yu Xuxia Meng Dabo Wang Pei Wang Ping Wang Identification of In Vivo Metabolites of Dictamnine in Mice Using HPLC-LTQ-Orbitrap Mass Spectrometry Journal of Analytical Methods in Chemistry |
| title | Identification of In Vivo Metabolites of Dictamnine in Mice Using HPLC-LTQ-Orbitrap Mass Spectrometry |
| title_full | Identification of In Vivo Metabolites of Dictamnine in Mice Using HPLC-LTQ-Orbitrap Mass Spectrometry |
| title_fullStr | Identification of In Vivo Metabolites of Dictamnine in Mice Using HPLC-LTQ-Orbitrap Mass Spectrometry |
| title_full_unstemmed | Identification of In Vivo Metabolites of Dictamnine in Mice Using HPLC-LTQ-Orbitrap Mass Spectrometry |
| title_short | Identification of In Vivo Metabolites of Dictamnine in Mice Using HPLC-LTQ-Orbitrap Mass Spectrometry |
| title_sort | identification of in vivo metabolites of dictamnine in mice using hplc ltq orbitrap mass spectrometry |
| url | http://dx.doi.org/10.1155/2018/3567647 |
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