An Entire Process Optimization Strategy for Comprehensive In Vivo Metabolite Profiling of Prucalopride in Rats Based on Ultra-Performance Liquid Chromatography With Q-Exactive Hybrid Quadrupole–Orbitrap High-Resolution Mass Spectrometry
Prucalopride was widely used for chronic constipation, which is difficult to be adequately relieved by laxatives in adult patients in clinic. Due to the difficulty in metabolite identification, metabolic process of prucalopride had not been investigated in vivo. In this study, an efficient strategy...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-05-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.610226/full |
| _version_ | 1818449841476337664 |
|---|---|
| author | Lihua Zuo Lihua Zuo Liwei Liu Liwei Liu Yantao Yang Yantao Yang Jie Yang Jie Yang Min Chen Huafeng Zhang Jian Kang Jian Kang Xiaojian Zhang Xiaojian Zhang Jiabo Wang Zhi Sun Zhi Sun |
| author_facet | Lihua Zuo Lihua Zuo Liwei Liu Liwei Liu Yantao Yang Yantao Yang Jie Yang Jie Yang Min Chen Huafeng Zhang Jian Kang Jian Kang Xiaojian Zhang Xiaojian Zhang Jiabo Wang Zhi Sun Zhi Sun |
| author_sort | Lihua Zuo |
| collection | DOAJ |
| description | Prucalopride was widely used for chronic constipation, which is difficult to be adequately relieved by laxatives in adult patients in clinic. Due to the difficulty in metabolite identification, metabolic process of prucalopride had not been investigated in vivo. In this study, an efficient strategy was proposed for comprehensive metabolite profiling of prucalopride after oral administration in rat plasma, urine, and feces samples. This strategy was composed of five steps. First, the samples at multiple time points after oral administration were collected to increase the representativeness of the samples. Second, different sample preparation methods were investigated to obtain superior extraction efficiency. Third, the raw data of test sample and blank sample were acquired using ultra-performance liquid chromatography with Q-Exactive hybrid quadrupole–orbitrap high-resolution accurate mass spectrometry under the positive and negative full-scan/dd MS2 mode. Fourth, combined mass defect filter with background subtraction model in soft of compound discovery, all peaks were constructed to filter potential metabolites after retention time alignment and ion filtration, which could remove large amounts of interference ions. Besides, it can predict potential biotransformation, promoting to understand how to metabolize the drug. This provides multiple possibilities and prevents us conjecturing the potential metabolites blindly. Finally, the verification procedure was implemented through exporting the structure and MS2 spectrum to the analytical tool of Mass Frontier. The proposed strategy significantly improved the targeted detection and identification for metabolites in vivo. A total of 47 metabolites were tentatively characterized in the plasma, urine, and feces samples after oral administration of prucalopride. This study could provide a valuable reference for systematic metabolite profile of drug in vivo. |
| first_indexed | 2024-12-14T20:41:49Z |
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| id | doaj.art-53dce5048b4c4bf1b21272ddcab07923 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-14T20:41:49Z |
| publishDate | 2021-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-53dce5048b4c4bf1b21272ddcab079232022-12-21T22:48:14ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-05-011210.3389/fphar.2021.610226610226An Entire Process Optimization Strategy for Comprehensive In Vivo Metabolite Profiling of Prucalopride in Rats Based on Ultra-Performance Liquid Chromatography With Q-Exactive Hybrid Quadrupole–Orbitrap High-Resolution Mass SpectrometryLihua Zuo0Lihua Zuo1Liwei Liu2Liwei Liu3Yantao Yang4Yantao Yang5Jie Yang6Jie Yang7Min Chen8Huafeng Zhang9Jian Kang10Jian Kang11Xiaojian Zhang12Xiaojian Zhang13Jiabo Wang14Zhi Sun15Zhi Sun16Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Engineering Research Center of Clinical Mass Spectrometry for Precision Medicine, Zhengzhou, ChinaDepartment of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Engineering Research Center of Clinical Mass Spectrometry for Precision Medicine, Zhengzhou, ChinaDepartment of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Engineering Research Center of Clinical Mass Spectrometry for Precision Medicine, Zhengzhou, ChinaDepartment of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Engineering Research Center of Clinical Mass Spectrometry for Precision Medicine, Zhengzhou, ChinaDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Orthopedics, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Engineering Research Center of Clinical Mass Spectrometry for Precision Medicine, Zhengzhou, ChinaDepartment of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Engineering Research Center of Clinical Mass Spectrometry for Precision Medicine, Zhengzhou, ChinaSchool of Traditional Chinese Medicine, Capital Medical University, Beijing, ChinaDepartment of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Engineering Research Center of Clinical Mass Spectrometry for Precision Medicine, Zhengzhou, ChinaPrucalopride was widely used for chronic constipation, which is difficult to be adequately relieved by laxatives in adult patients in clinic. Due to the difficulty in metabolite identification, metabolic process of prucalopride had not been investigated in vivo. In this study, an efficient strategy was proposed for comprehensive metabolite profiling of prucalopride after oral administration in rat plasma, urine, and feces samples. This strategy was composed of five steps. First, the samples at multiple time points after oral administration were collected to increase the representativeness of the samples. Second, different sample preparation methods were investigated to obtain superior extraction efficiency. Third, the raw data of test sample and blank sample were acquired using ultra-performance liquid chromatography with Q-Exactive hybrid quadrupole–orbitrap high-resolution accurate mass spectrometry under the positive and negative full-scan/dd MS2 mode. Fourth, combined mass defect filter with background subtraction model in soft of compound discovery, all peaks were constructed to filter potential metabolites after retention time alignment and ion filtration, which could remove large amounts of interference ions. Besides, it can predict potential biotransformation, promoting to understand how to metabolize the drug. This provides multiple possibilities and prevents us conjecturing the potential metabolites blindly. Finally, the verification procedure was implemented through exporting the structure and MS2 spectrum to the analytical tool of Mass Frontier. The proposed strategy significantly improved the targeted detection and identification for metabolites in vivo. A total of 47 metabolites were tentatively characterized in the plasma, urine, and feces samples after oral administration of prucalopride. This study could provide a valuable reference for systematic metabolite profile of drug in vivo.https://www.frontiersin.org/articles/10.3389/fphar.2021.610226/fullprucalopridemetabolite identificationhigh-resolution mass spectrometrythe entire and novel strategymetabolic network |
| spellingShingle | Lihua Zuo Lihua Zuo Liwei Liu Liwei Liu Yantao Yang Yantao Yang Jie Yang Jie Yang Min Chen Huafeng Zhang Jian Kang Jian Kang Xiaojian Zhang Xiaojian Zhang Jiabo Wang Zhi Sun Zhi Sun An Entire Process Optimization Strategy for Comprehensive In Vivo Metabolite Profiling of Prucalopride in Rats Based on Ultra-Performance Liquid Chromatography With Q-Exactive Hybrid Quadrupole–Orbitrap High-Resolution Mass Spectrometry Frontiers in Pharmacology prucalopride metabolite identification high-resolution mass spectrometry the entire and novel strategy metabolic network |
| title | An Entire Process Optimization Strategy for Comprehensive In Vivo Metabolite Profiling of Prucalopride in Rats Based on Ultra-Performance Liquid Chromatography With Q-Exactive Hybrid Quadrupole–Orbitrap High-Resolution Mass Spectrometry |
| title_full | An Entire Process Optimization Strategy for Comprehensive In Vivo Metabolite Profiling of Prucalopride in Rats Based on Ultra-Performance Liquid Chromatography With Q-Exactive Hybrid Quadrupole–Orbitrap High-Resolution Mass Spectrometry |
| title_fullStr | An Entire Process Optimization Strategy for Comprehensive In Vivo Metabolite Profiling of Prucalopride in Rats Based on Ultra-Performance Liquid Chromatography With Q-Exactive Hybrid Quadrupole–Orbitrap High-Resolution Mass Spectrometry |
| title_full_unstemmed | An Entire Process Optimization Strategy for Comprehensive In Vivo Metabolite Profiling of Prucalopride in Rats Based on Ultra-Performance Liquid Chromatography With Q-Exactive Hybrid Quadrupole–Orbitrap High-Resolution Mass Spectrometry |
| title_short | An Entire Process Optimization Strategy for Comprehensive In Vivo Metabolite Profiling of Prucalopride in Rats Based on Ultra-Performance Liquid Chromatography With Q-Exactive Hybrid Quadrupole–Orbitrap High-Resolution Mass Spectrometry |
| title_sort | entire process optimization strategy for comprehensive in vivo metabolite profiling of prucalopride in rats based on ultra performance liquid chromatography with q exactive hybrid quadrupole orbitrap high resolution mass spectrometry |
| topic | prucalopride metabolite identification high-resolution mass spectrometry the entire and novel strategy metabolic network |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.610226/full |
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