Ioanna Tsiara, Mario S P Correia, Fan Yang, Weiming Zeng, Pauline Seeburger, Belén Hervás Povo, Iben Lundgaard, Manuel Menéndez-González, Miroslav Vujasinovic, J-Matthias Löhr, Daniel Globisch
{"title":"人类血浆、粪便和脑脊液样本中葡萄糖醛酸苷的全球代谢组学分析","authors":"Ioanna Tsiara, Mario S P Correia, Fan Yang, Weiming Zeng, Pauline Seeburger, Belén Hervás Povo, Iben Lundgaard, Manuel Menéndez-González, Miroslav Vujasinovic, J-Matthias Löhr, Daniel Globisch","doi":"10.1007/s00216-025-06082-w","DOIUrl":null,"url":null,"abstract":"<p><p>Glucuronidation is the major phase II biotransformation reaction that facilitates the clearance of exogenous compounds from the human body. Glucuronidated metabolites have been investigated in urine samples at a broad scale; however, their characterization in other human biospecimens is underexplored. Our study has now performed a comprehensive profiling of glucuronides in plasma, fecal, and cerebrospinal fluid (CSF) of humans. We performed a mass spectrometry-based analysis that combines enzymatic hydrolysis with a β-glucuronidase to selectively cleave the glucuronic acid moiety, a developed in-house glucuronide identification pipeline, and enzymatic synthesis of standard metabolites. In total, we identified 32 glucuronidated metabolites across the three sample types in both negative and positive mass spectrometry ionization modes using advanced MS/MS fragmentation analysis. We have utilized a straightforward enzymatic synthesis of glucuronidated metabolites for annotation at the highest confidence level. Among the identified conjugates, we detected glucuronides of different compound classes including drugs, bile acid derivatives, steroid conjugates, and phenolic compounds. Unexpectedly, we validated the glucuronides of acetaminophen and propofol in CSF samples, the latter representing a novel observation that highlights the importance of investigating phase II metabolites in uncommon sample types.</p>","PeriodicalId":462,"journal":{"name":"Analytical and Bioanalytical Chemistry","volume":" ","pages":""},"PeriodicalIF":3.8000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Global metabolomics profiling of glucuronides in human plasma, fecal, and cerebrospinal fluid samples.\",\"authors\":\"Ioanna Tsiara, Mario S P Correia, Fan Yang, Weiming Zeng, Pauline Seeburger, Belén Hervás Povo, Iben Lundgaard, Manuel Menéndez-González, Miroslav Vujasinovic, J-Matthias Löhr, Daniel Globisch\",\"doi\":\"10.1007/s00216-025-06082-w\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Glucuronidation is the major phase II biotransformation reaction that facilitates the clearance of exogenous compounds from the human body. 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Among the identified conjugates, we detected glucuronides of different compound classes including drugs, bile acid derivatives, steroid conjugates, and phenolic compounds. Unexpectedly, we validated the glucuronides of acetaminophen and propofol in CSF samples, the latter representing a novel observation that highlights the importance of investigating phase II metabolites in uncommon sample types.</p>\",\"PeriodicalId\":462,\"journal\":{\"name\":\"Analytical and Bioanalytical Chemistry\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.8000,\"publicationDate\":\"2025-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Analytical and Bioanalytical Chemistry\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://doi.org/10.1007/s00216-025-06082-w\",\"RegionNum\":2,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMICAL RESEARCH METHODS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Analytical and Bioanalytical Chemistry","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1007/s00216-025-06082-w","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
Global metabolomics profiling of glucuronides in human plasma, fecal, and cerebrospinal fluid samples.
Glucuronidation is the major phase II biotransformation reaction that facilitates the clearance of exogenous compounds from the human body. Glucuronidated metabolites have been investigated in urine samples at a broad scale; however, their characterization in other human biospecimens is underexplored. Our study has now performed a comprehensive profiling of glucuronides in plasma, fecal, and cerebrospinal fluid (CSF) of humans. We performed a mass spectrometry-based analysis that combines enzymatic hydrolysis with a β-glucuronidase to selectively cleave the glucuronic acid moiety, a developed in-house glucuronide identification pipeline, and enzymatic synthesis of standard metabolites. In total, we identified 32 glucuronidated metabolites across the three sample types in both negative and positive mass spectrometry ionization modes using advanced MS/MS fragmentation analysis. We have utilized a straightforward enzymatic synthesis of glucuronidated metabolites for annotation at the highest confidence level. Among the identified conjugates, we detected glucuronides of different compound classes including drugs, bile acid derivatives, steroid conjugates, and phenolic compounds. Unexpectedly, we validated the glucuronides of acetaminophen and propofol in CSF samples, the latter representing a novel observation that highlights the importance of investigating phase II metabolites in uncommon sample types.
期刊介绍:
Analytical and Bioanalytical Chemistry’s mission is the rapid publication of excellent and high-impact research articles on fundamental and applied topics of analytical and bioanalytical measurement science. Its scope is broad, and ranges from novel measurement platforms and their characterization to multidisciplinary approaches that effectively address important scientific problems. The Editors encourage submissions presenting innovative analytical research in concept, instrumentation, methods, and/or applications, including: mass spectrometry, spectroscopy, and electroanalysis; advanced separations; analytical strategies in “-omics” and imaging, bioanalysis, and sampling; miniaturized devices, medical diagnostics, sensors; analytical characterization of nano- and biomaterials; chemometrics and advanced data analysis.