Comprehensive characterization of narirutin metabolites in vitro and in vivo based on Analogous-Core recursion analysis strategy using UHPLC-Q-Exactive Orbitrap MS/MS
Narirutin, extracted from the dried ripe pericarp of Rutaceae orange and its cultivated varieties, is a dihydroflavone compound with various biological activities and pharmacological effects. So far as we know, the metabolism profiling of narirutin has been insufficient until now. In the present stu...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-08-01
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| Series: | Arabian Journal of Chemistry |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1878535223004112 |
| _version_ | 1797804016981245952 |
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| author | Shuyi Song Hongyan Zhou Xianming Lan Xiaoqing Yuan Yanan Li Shuteng Huang Zhibin Wang Jiayu Zhang |
| author_facet | Shuyi Song Hongyan Zhou Xianming Lan Xiaoqing Yuan Yanan Li Shuteng Huang Zhibin Wang Jiayu Zhang |
| author_sort | Shuyi Song |
| collection | DOAJ |
| description | Narirutin, extracted from the dried ripe pericarp of Rutaceae orange and its cultivated varieties, is a dihydroflavone compound with various biological activities and pharmacological effects. So far as we know, the metabolism profiling of narirutin has been insufficient until now. In the present study, an efficient method was employed to perform rapid analysis and identification of narirutin metabolites by using ultra-high performance liquid chromatography quadrupole exactive orbitrap MS/MS (UHPLC-Q-Exactive Orbitrap MS/MS) combined with an analogous core recursion (ACR) analysis strategy. Firstly, according to the basic core structure of the dihydroflavonoid, the cleavage mode and fragmentation ions of narirutin were summarized. Secondly, based on the difference of the substituent groups, the fragment ions of narirutin were preliminarily inferred and verified by the secondary mass spectra of its standard compound. Thirdly, the fragment ions of narirutin in positive and negative ion modes were summarized to provide a basis for the identification of metabolites. Fourthly, candidate metabolites were accurately and tentatively identified according to the cleavage law of mass spectrometry, literature reports, comparison of reference substances, and especially the diagnostic fragment ion clusters (DFICs) and characteristic suggestive ions (CSIs) deduced preliminarily. Finally, a total of 46 metabolites (30 in vivo and 19 in vitro), including prototype drugs were identified based on the ACR analysis strategy, chromatographic retention behavior of metabolites, corresponding ClogP value and accurate molecular weight. Among them, 22 metabolites were discovered in rats plasma, 12 in urine, 4 in liver tissue, 19 in liver microsomes, respectively. Additionally, metabolites relative contents were also studied by extracted ion chromatography (EIC) method. Our result also illustrated that narirutin primarily underwent glucuronidation, sulfation, glutathione binding, deglycosylation, oxidation, reduction, methylation, hydroxylation, ring-opening and their composite reactions. A novel strategy was constructed to comprehensively elucidate the biotransformation pathways of narirutin in vitro and in vivo, and a systematic metabolic profile of narirutin was generated. This study provided a great reference for further understanding of the biotransformation pathways and guiding for clinical application of narirutin. |
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| institution | Directory Open Access Journal |
| issn | 1878-5352 |
| language | English |
| last_indexed | 2024-03-13T05:29:46Z |
| publishDate | 2023-08-01 |
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| series | Arabian Journal of Chemistry |
| spelling | doaj.art-bb3dfa54936347848b68080026aca6f22023-06-15T04:55:02ZengElsevierArabian Journal of Chemistry1878-53522023-08-01168104949Comprehensive characterization of narirutin metabolites in vitro and in vivo based on Analogous-Core recursion analysis strategy using UHPLC-Q-Exactive Orbitrap MS/MSShuyi Song0Hongyan Zhou1Xianming Lan2Xiaoqing Yuan3Yanan Li4Shuteng Huang5Zhibin Wang6Jiayu Zhang7School of Pharmacy, Binzhou Medical University, 264003 Yantai, Shandong, ChinaSchool of Pharmacy, Shandong University of Traditional Chinese Medicine, 250300 Jinan, Shandong, ChinaSchool of Pharmacy, Binzhou Medical University, 264003 Yantai, Shandong, ChinaSchool of Pharmacy, Binzhou Medical University, 264003 Yantai, Shandong, ChinaSchool of Pharmacy, Shandong University of Traditional Chinese Medicine, 250300 Jinan, Shandong, ChinaSchool of Pharmacy, Binzhou Medical University, 264003 Yantai, Shandong, ChinaTongrentang Research Institute, Beijing 100079, China; Corresponding authors.School of Pharmacy, Binzhou Medical University, 264003 Yantai, Shandong, China; Corresponding authors.Narirutin, extracted from the dried ripe pericarp of Rutaceae orange and its cultivated varieties, is a dihydroflavone compound with various biological activities and pharmacological effects. So far as we know, the metabolism profiling of narirutin has been insufficient until now. In the present study, an efficient method was employed to perform rapid analysis and identification of narirutin metabolites by using ultra-high performance liquid chromatography quadrupole exactive orbitrap MS/MS (UHPLC-Q-Exactive Orbitrap MS/MS) combined with an analogous core recursion (ACR) analysis strategy. Firstly, according to the basic core structure of the dihydroflavonoid, the cleavage mode and fragmentation ions of narirutin were summarized. Secondly, based on the difference of the substituent groups, the fragment ions of narirutin were preliminarily inferred and verified by the secondary mass spectra of its standard compound. Thirdly, the fragment ions of narirutin in positive and negative ion modes were summarized to provide a basis for the identification of metabolites. Fourthly, candidate metabolites were accurately and tentatively identified according to the cleavage law of mass spectrometry, literature reports, comparison of reference substances, and especially the diagnostic fragment ion clusters (DFICs) and characteristic suggestive ions (CSIs) deduced preliminarily. Finally, a total of 46 metabolites (30 in vivo and 19 in vitro), including prototype drugs were identified based on the ACR analysis strategy, chromatographic retention behavior of metabolites, corresponding ClogP value and accurate molecular weight. Among them, 22 metabolites were discovered in rats plasma, 12 in urine, 4 in liver tissue, 19 in liver microsomes, respectively. Additionally, metabolites relative contents were also studied by extracted ion chromatography (EIC) method. Our result also illustrated that narirutin primarily underwent glucuronidation, sulfation, glutathione binding, deglycosylation, oxidation, reduction, methylation, hydroxylation, ring-opening and their composite reactions. A novel strategy was constructed to comprehensively elucidate the biotransformation pathways of narirutin in vitro and in vivo, and a systematic metabolic profile of narirutin was generated. This study provided a great reference for further understanding of the biotransformation pathways and guiding for clinical application of narirutin.http://www.sciencedirect.com/science/article/pii/S1878535223004112NarirutinUHPLC-Q-Exactive Orbitrap MS/MSMetabolitesAnalogous-Core Recursion analysis strategyIn vitro and in vivo |
| spellingShingle | Shuyi Song Hongyan Zhou Xianming Lan Xiaoqing Yuan Yanan Li Shuteng Huang Zhibin Wang Jiayu Zhang Comprehensive characterization of narirutin metabolites in vitro and in vivo based on Analogous-Core recursion analysis strategy using UHPLC-Q-Exactive Orbitrap MS/MS Arabian Journal of Chemistry Narirutin UHPLC-Q-Exactive Orbitrap MS/MS Metabolites Analogous-Core Recursion analysis strategy In vitro and in vivo |
| title | Comprehensive characterization of narirutin metabolites in vitro and in vivo based on Analogous-Core recursion analysis strategy using UHPLC-Q-Exactive Orbitrap MS/MS |
| title_full | Comprehensive characterization of narirutin metabolites in vitro and in vivo based on Analogous-Core recursion analysis strategy using UHPLC-Q-Exactive Orbitrap MS/MS |
| title_fullStr | Comprehensive characterization of narirutin metabolites in vitro and in vivo based on Analogous-Core recursion analysis strategy using UHPLC-Q-Exactive Orbitrap MS/MS |
| title_full_unstemmed | Comprehensive characterization of narirutin metabolites in vitro and in vivo based on Analogous-Core recursion analysis strategy using UHPLC-Q-Exactive Orbitrap MS/MS |
| title_short | Comprehensive characterization of narirutin metabolites in vitro and in vivo based on Analogous-Core recursion analysis strategy using UHPLC-Q-Exactive Orbitrap MS/MS |
| title_sort | comprehensive characterization of narirutin metabolites in vitro and in vivo based on analogous core recursion analysis strategy using uhplc q exactive orbitrap ms ms |
| topic | Narirutin UHPLC-Q-Exactive Orbitrap MS/MS Metabolites Analogous-Core Recursion analysis strategy In vitro and in vivo |
| url | http://www.sciencedirect.com/science/article/pii/S1878535223004112 |
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