Integrated Solid-Phase Extraction, Ultra-High-Performance Liquid Chromatography–Quadrupole-Orbitrap High-Resolution Mass Spectrometry, and Multidimensional Data-Mining Techniques to Unravel the Metabolic Network of Dehydrocostus Lactone in Rats
Dehydrocostus lactone (DL) is among the representative ingredients of traditional Chinese medicine (TCM), with excellent anticancer, antibacterial, and anti-inflammatory activities. In this study, an advanced strategy based on ultra-high-performance liquid chromatography–quadrupole-Orbitrap high-res...
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MDPI AG
2022-11-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/22/7688 |
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| author | Yingying Tian Beibei Ma Chuang Liu Xinyue Zhao Shangyue Yu Yilin Li Shiqiu Tian Hailuan Pei Zijian Wang Zeping Zuo Zhibin Wang |
| author_facet | Yingying Tian Beibei Ma Chuang Liu Xinyue Zhao Shangyue Yu Yilin Li Shiqiu Tian Hailuan Pei Zijian Wang Zeping Zuo Zhibin Wang |
| author_sort | Yingying Tian |
| collection | DOAJ |
| description | Dehydrocostus lactone (DL) is among the representative ingredients of traditional Chinese medicine (TCM), with excellent anticancer, antibacterial, and anti-inflammatory activities. In this study, an advanced strategy based on ultra-high-performance liquid chromatography–quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC–Q-Orbitrap HRMS) was integrated to comprehensively explore the metabolic fate of DL in rats. First, prior to data collection, all biological samples (plasma, urine, and feces) were concentrated and purified using solid-phase extraction (SPE) pre-treatment technology. Then, during data collection, in the full-scan (FS) data-dependent acquisition mode, FS-ddMS<sup>2</sup> was intelligently combined with FS-parent ion list (PIL)-dynamic exclusion (DE) means for targeted monitoring and deeper capture of more low-abundance ions of interest. After data acquisition, data-mining techniques such as high-resolution extracted ion chromatograms (HREICs), multiple mass defect filters (MMDFs), diagnostic product ions (DPIs), and neutral loss fragments (NLFs) were incorporated to extensively screen and profile all the metabolites in multiple dimensions. As a result, a total of 71 metabolites of DL (parent drug included) were positively or tentatively identified. The results suggested that DL in vivo mainly underwent hydration, hydroxylation, dihydrodiolation, sulfonation, methylation, dehydrogenation, dehydration, N-acetylcysteine conjugation, cysteine conjugation, glutathione conjugation, glycine conjugation, taurine conjugation, etc. With these inferences, we successfully mapped the “stepwise radiation” metabolic network of DL in rats, where several drug metabolism clusters (DMCs) were discovered. In conclusion, not only did we provide a refined strategy for inhibiting matrix effects and fully screening major-to-trace metabolites, but also give substantial data reference for mechanism investigation, in vivo distribution visualization, and safety evaluation of DL. |
| first_indexed | 2024-03-09T18:07:57Z |
| format | Article |
| id | doaj.art-68d4b0a30d8e4523bfbcd303d890ec0c |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T18:07:57Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-68d4b0a30d8e4523bfbcd303d890ec0c2023-11-24T09:19:27ZengMDPI AGMolecules1420-30492022-11-012722768810.3390/molecules27227688Integrated Solid-Phase Extraction, Ultra-High-Performance Liquid Chromatography–Quadrupole-Orbitrap High-Resolution Mass Spectrometry, and Multidimensional Data-Mining Techniques to Unravel the Metabolic Network of Dehydrocostus Lactone in RatsYingying Tian0Beibei Ma1Chuang Liu2Xinyue Zhao3Shangyue Yu4Yilin Li5Shiqiu Tian6Hailuan Pei7Zijian Wang8Zeping Zuo9Zhibin Wang10School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, ChinaResearch Institute of Beijing Tongrentang Co., Ltd., Beijing 100079, ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, ChinaResearch Institute of Beijing Tongrentang Co., Ltd., Beijing 100079, ChinaResearch Institute of Beijing Tongrentang Co., Ltd., Beijing 100079, ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, ChinaDehydrocostus lactone (DL) is among the representative ingredients of traditional Chinese medicine (TCM), with excellent anticancer, antibacterial, and anti-inflammatory activities. In this study, an advanced strategy based on ultra-high-performance liquid chromatography–quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC–Q-Orbitrap HRMS) was integrated to comprehensively explore the metabolic fate of DL in rats. First, prior to data collection, all biological samples (plasma, urine, and feces) were concentrated and purified using solid-phase extraction (SPE) pre-treatment technology. Then, during data collection, in the full-scan (FS) data-dependent acquisition mode, FS-ddMS<sup>2</sup> was intelligently combined with FS-parent ion list (PIL)-dynamic exclusion (DE) means for targeted monitoring and deeper capture of more low-abundance ions of interest. After data acquisition, data-mining techniques such as high-resolution extracted ion chromatograms (HREICs), multiple mass defect filters (MMDFs), diagnostic product ions (DPIs), and neutral loss fragments (NLFs) were incorporated to extensively screen and profile all the metabolites in multiple dimensions. As a result, a total of 71 metabolites of DL (parent drug included) were positively or tentatively identified. The results suggested that DL in vivo mainly underwent hydration, hydroxylation, dihydrodiolation, sulfonation, methylation, dehydrogenation, dehydration, N-acetylcysteine conjugation, cysteine conjugation, glutathione conjugation, glycine conjugation, taurine conjugation, etc. With these inferences, we successfully mapped the “stepwise radiation” metabolic network of DL in rats, where several drug metabolism clusters (DMCs) were discovered. In conclusion, not only did we provide a refined strategy for inhibiting matrix effects and fully screening major-to-trace metabolites, but also give substantial data reference for mechanism investigation, in vivo distribution visualization, and safety evaluation of DL.https://www.mdpi.com/1420-3049/27/22/7688dehydrocostus lactone (DL)UHPLC–Q-Orbitrap HRMSsolid-phase extraction (SPE)data-mining techniquesmetabolic network |
| spellingShingle | Yingying Tian Beibei Ma Chuang Liu Xinyue Zhao Shangyue Yu Yilin Li Shiqiu Tian Hailuan Pei Zijian Wang Zeping Zuo Zhibin Wang Integrated Solid-Phase Extraction, Ultra-High-Performance Liquid Chromatography–Quadrupole-Orbitrap High-Resolution Mass Spectrometry, and Multidimensional Data-Mining Techniques to Unravel the Metabolic Network of Dehydrocostus Lactone in Rats Molecules dehydrocostus lactone (DL) UHPLC–Q-Orbitrap HRMS solid-phase extraction (SPE) data-mining techniques metabolic network |
| title | Integrated Solid-Phase Extraction, Ultra-High-Performance Liquid Chromatography–Quadrupole-Orbitrap High-Resolution Mass Spectrometry, and Multidimensional Data-Mining Techniques to Unravel the Metabolic Network of Dehydrocostus Lactone in Rats |
| title_full | Integrated Solid-Phase Extraction, Ultra-High-Performance Liquid Chromatography–Quadrupole-Orbitrap High-Resolution Mass Spectrometry, and Multidimensional Data-Mining Techniques to Unravel the Metabolic Network of Dehydrocostus Lactone in Rats |
| title_fullStr | Integrated Solid-Phase Extraction, Ultra-High-Performance Liquid Chromatography–Quadrupole-Orbitrap High-Resolution Mass Spectrometry, and Multidimensional Data-Mining Techniques to Unravel the Metabolic Network of Dehydrocostus Lactone in Rats |
| title_full_unstemmed | Integrated Solid-Phase Extraction, Ultra-High-Performance Liquid Chromatography–Quadrupole-Orbitrap High-Resolution Mass Spectrometry, and Multidimensional Data-Mining Techniques to Unravel the Metabolic Network of Dehydrocostus Lactone in Rats |
| title_short | Integrated Solid-Phase Extraction, Ultra-High-Performance Liquid Chromatography–Quadrupole-Orbitrap High-Resolution Mass Spectrometry, and Multidimensional Data-Mining Techniques to Unravel the Metabolic Network of Dehydrocostus Lactone in Rats |
| title_sort | integrated solid phase extraction ultra high performance liquid chromatography quadrupole orbitrap high resolution mass spectrometry and multidimensional data mining techniques to unravel the metabolic network of dehydrocostus lactone in rats |
| topic | dehydrocostus lactone (DL) UHPLC–Q-Orbitrap HRMS solid-phase extraction (SPE) data-mining techniques metabolic network |
| url | https://www.mdpi.com/1420-3049/27/22/7688 |
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