{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T11:16:28Z","timestamp":1789470988352,"version":"build-2803163510"},"reference-count":34,"publisher":"American Chemical Society (ACS)","issue":"41","license":[{"start":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:00:00Z","timestamp":1760054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["FWF P33188"],"award-info":[{"award-number":["FWF P33188"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010663","name":"H2020 European Research Council","doi-asserted-by":"publisher","award":["101043321"],"award-info":[{"award-number":["101043321"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The exposome encompasses environmental exposures throughout life and significantly impacts health and disease. Exposure chemicals, present at trace levels, are frequently quantified using targeted LC\u2013MS\/MS. Many existing methods are limited to a narrow range of analyte classes or lack sufficient sensitivity for exposomic analyses, and applicability to large sample cohorts for exposome-wide association studies (ExWAS) remains to be demonstrated. Here, we present a scalable, fit-for-purpose next-generation human biomonitoring (HBM) workflow for analyzing &amp;gt;230 biomarkers in urine, plasma, and serum using solid-phase extraction in 96-well plates and LC\u2013MS\/MS. Moreover, a complementary conceptual framework for validation criteria of assays designed to analyze large panels of highly diverse compounds at trace levels is proposed. Method robustness was evaluated, demonstrating extraction recovery (60\u2013130%), matrix effects (SSE, 60\u2013130%), inter-\/intraday precision (RSD &amp;lt;30%), and high sensitivity (limit of detection &amp;lt;0.1 ng\/mL) for 59\u201380% of the analytes across the investigated biological matrices. To showcase the method\u2019s applicability in epidemiological studies, 200 urine samples from pregnant women in a longitudinal pregnancy cohort were analyzed. More than 100 analytes including PFAS, drugs, air pollutants, pesticides, flame retardants, mycotoxins, industrial products, food processing contaminants, plastics-related chemicals, and phytotoxins, were detected, several for the first time in a U.S. urinary biomonitoring study. With its broad analyte coverage, ultimate sensitivity, robustness, and high sample throughput, this method meets the performance requirements for future large-scale ExWAS applications in public and personalized prevention research.<\/jats:p>","DOI":"10.1021\/acs.est.5c04458","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:34:12Z","timestamp":1760103252000},"page":"21818-21829","source":"Crossref","is-referenced-by-count":18,"title":["Quantitative\nExposomics Targeting over 200 Toxicants\nand Key Biomarkers at the Picomolar Level"],"prefix":"10.1021","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5853-7431","authenticated-orcid":true,"given":"Yunyun","family":"Gu","sequence":"first","affiliation":[{"name":"University of Vienna , , Wa\u0308hringer Stra\u00dfe 42 , ,","place":["Vienna, Austria, 1090"]},{"name":"University of Vienna , , Wa\u0308hringer Stra\u00dfe 42 , ,","place":["Vienna, Austria, 1090"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9839-0542","authenticated-orcid":true,"given":"Max L.","family":"Feuerstein","sequence":"additional","affiliation":[{"name":"University of Vienna , , Wa\u0308hringer Stra\u00dfe 42 , ,","place":["Vienna, Austria, 1090"]},{"name":"Research Infrastructure and National EIRENE Node , , ,","place":["Vienna, Austria, 1090"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dillon T.","family":"Lloyd","sequence":"additional","affiliation":[{"name":"Harvard Medical School , , , ,","place":["Boston, Massachusetts, United States, 02115"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8756-8525","authenticated-orcid":true,"given":"Chirag J.","family":"Patel","sequence":"additional","affiliation":[{"name":"Harvard Medical School , , , ,","place":["Boston, Massachusetts, United States, 02115"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline H.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Yale School of Public Health , , , ,","place":["New Haven, Connecticut, United States, 06510"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6104-0706","authenticated-orcid":true,"given":"Benedikt","family":"Warth","sequence":"additional","affiliation":[{"name":"University of Vienna , , Wa\u0308hringer Stra\u00dfe 42 , ,","place":["Vienna, Austria, 1090"]},{"name":"University of Vienna , , Wa\u0308hringer Stra\u00dfe 42 , ,","place":["Vienna, Austria, 1090"]},{"name":"Research Infrastructure and National EIRENE Node , , ,","place":["Vienna, Austria, 1090"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2025,10,10]]},"reference":[{"key":"2026081812155538400_cit1","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1186\/s12940-020-00670-2","article-title":"Environmental chemicals, breast cancer progression\nand drug resistance","volume":"19","author":"Koual","year":"2020","journal-title":"Environ. Health"},{"issue":"8","key":"2026081812155538400_cit2","doi-asserted-by":"publisher","first-page":"1847","DOI":"10.1158\/1055-9965.EPI-05-0456","article-title":"Complementing\nthe genome with an exposome: the outstanding challenge of environmental\nexposure measurement in molecular epidemiology","volume":"14","author":"Wild","year":"2005","journal-title":"Cancer Epidemiol. Biomarkers Prev."},{"issue":"1","key":"2026081812155538400_cit3","doi-asserted-by":"publisher","first-page":"2268","DOI":"10.1038\/s41467-024-46595-z","article-title":"An exposome atlas of serum reveals the risk of chronic diseases in\nthe Chinese population","volume":"15","author":"You","year":"2024","journal-title":"Nat. Commun."},{"issue":"29","key":"2026081812155538400_cit4","doi-asserted-by":"publisher","first-page":"12784","DOI":"10.1021\/acs.est.4c01156","article-title":"High-resolution\nmass\nspectrometry for human exposomics: Expanding chemical space coverage","volume":"58","author":"Lai","year":"2024","journal-title":"Environ. Sci. Technol."},{"issue":"28","key":"2026081812155538400_cit5","doi-asserted-by":"publisher","first-page":"10173","DOI":"10.1021\/acs.est.3c00663","article-title":"Phospholipid\nremoval for enhanced chemical exposomics in human plasma","volume":"57","author":"Sdougkou","year":"2023","journal-title":"Environ. Sci. Technol."},{"issue":"29","key":"2026081812155538400_cit6","doi-asserted-by":"publisher","first-page":"7297","DOI":"10.1007\/s00216-023-04998-9","article-title":"Comprehensive profiling and semi-quantification\nof exogenous chemicals in human urine using HRMS-based strategies","volume":"415","author":"Gutie\u0301rrez-Marti\u0301n","year":"2023","journal-title":"Anal. Bioanal. Chem."},{"issue":"1","key":"2026081812155538400_cit7","doi-asserted-by":"publisher","first-page":"2653","DOI":"10.1038\/s41467-022-30204-y","article-title":"Next-generation biomonitoring of\nthe early-life chemical exposome\nin neonatal and infant development","volume":"13","author":"Jamnik","year":"2022","journal-title":"Nat. Commun."},{"issue":"19","key":"2026081812155538400_cit8","doi-asserted-by":"publisher","first-page":"5943","DOI":"10.1007\/s00216-022-04159-4","article-title":"Validated single\nurinary assay designed for exposomic multi-class biomarkers of common\nenvironmental exposures","volume":"414","author":"Jagani","year":"2022","journal-title":"Anal. Bioanal. Chem."},{"issue":"4","key":"2026081812155538400_cit9","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1038\/s41370-023-00574-6","article-title":"Non-targeted\nanalysis (NTA) and suspect screening\nanalysis (SSA): a review of examining the chemical exposome","volume":"33","author":"Manz","year":"2023","journal-title":"J. Expo. Sci. Environ. Epidemiol."},{"key":"2026081812155538400_cit10","doi-asserted-by":"publisher","first-page":"109081","DOI":"10.1016\/j.envint.2024.109081","article-title":"Longitudinal biomonitoring\nof mycotoxin exposure during pregnancy\nin the Yale pregnancy Outcome Prediction study","volume":"194","author":"Krausova\u0301","year":"2024","journal-title":"Environ. Int."},{"key":"2026081812155538400_cit11","doi-asserted-by":"publisher","first-page":"105845","DOI":"10.1016\/j.envint.2020.105845","article-title":"Longitudinal assessment\nof mycotoxin co-exposures in exclusively breastfed infants","volume":"142","author":"Braun","year":"2020","journal-title":"Environ. Int."},{"issue":"17","key":"2026081812155538400_cit12","doi-asserted-by":"publisher","first-page":"11334","DOI":"10.1021\/acs.analchem.9b02446","article-title":"A Generic\nLiquid Chromatography-Tandem\nMass Spectrometry Exposome Method for the Determination of Xenoestrogens\nin Biological Matrices","volume":"91","author":"Preindl","year":"2019","journal-title":"Anal. Chem."},{"issue":"36","key":"2026081812155538400_cit13","doi-asserted-by":"publisher","first-page":"13408","DOI":"10.1021\/acs.est.3c04492","article-title":"Target Exposome\nfor Characterizing Early Gestational Exposure to Contaminants of Emerging\nConcern and Association with Gestational Diabetes Mellitus","volume":"57","author":"Huang","year":"2023","journal-title":"Environ. Sci. Technol."},{"issue":"2","key":"2026081812155538400_cit14","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1021\/acs.analchem.1c03638","article-title":"Comprehensive evaluation\nof blood plasma and serum sample preparations for HRMS-based chemical\nexposomics: overlaps and specificities","volume":"94","author":"Chaker","year":"2022","journal-title":"Anal.\nChem."},{"key":"2026081812155538400_cit15","doi-asserted-by":"publisher","first-page":"117151","DOI":"10.1016\/j.trac.2023.117151","article-title":"Sample preparation\nstrategies for\nmass spectrometry analysis in human exposome research: Current status\nand future perspectives","volume":"166","author":"Gu","year":"2023","journal-title":"Trends Anal. Chem."},{"key":"2026081812155538400_cit16","doi-asserted-by":"publisher","first-page":"6075","DOI":"10.1021\/acs.analchem.4c06177","article-title":"High-Throughput Solid\nPhase Extraction\nfor Targeted and Nontargeted Exposomics","volume":"97","author":"Gu","year":"2025","journal-title":"Anal.\nChem."},{"key":"2026081812155538400_cit17","first-page":"84","volume-title":"Commission Implementing\nRegulation (EU) 2021\/808\nof 22 March 2021 on the Performance of Analytical Methods for Residues\nof Pharmacologically Active Substances Used in food-producing Animals\nand on the Interpretation of Results as Well as on the Methods to\nbe Used for Sampling and Repealing Decisions 2002\/657\/EC and 98\/179\/EC","author":"European\nCommission.","year":"2021"},{"issue":"6719","key":"2026081812155538400_cit18","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1126\/science.adq0336","article-title":"Neurotoxic mixture\neffects of chemicals extracted from blood of pregnant women","volume":"386","author":"Braun","year":"2024","journal-title":"Science"},{"issue":"1","key":"2026081812155538400_cit19","doi-asserted-by":"publisher","first-page":"7024","DOI":"10.1038\/s41467-022-34422-2","article-title":"Multi-omics signatures of the human early life exposome","volume":"13","author":"Maitre","year":"2022","journal-title":"Nat. Commun."},{"key":"2026081812155538400_cit20","doi-asserted-by":"publisher","first-page":"108981","DOI":"10.1016\/j.envint.2024.108981","article-title":"Pesticide\nresidues and polyphenols in urine-A combined LC-HRMS screening to\nreveal intake patterns","volume":"191","author":"Huber","year":"2024","journal-title":"Environ. Int."},{"key":"2026081812155538400_cit21","doi-asserted-by":"publisher","first-page":"4369","DOI":"10.1007\/s00216-024-05374-x","article-title":"Scaling up\na targeted\nexposome LC-MS\/MS biomonitoring method by incorporating veterinary\ndrugs and pesticides","volume":"416","author":"Hossain","year":"2024","journal-title":"Anal. Bioanal. Chem."},{"issue":"Pt 2","key":"2026081812155538400_cit22","doi-asserted-by":"publisher","first-page":"132226","DOI":"10.1016\/j.chemosphere.2021.132226","article-title":"Mycotoxin-mixture\nassessment in mother-infant\npairs in Nigeria: From mothers\u2019 meal to infants\u2019 urine","volume":"287","author":"Braun","year":"2022","journal-title":"Chemosphere"},{"issue":"13","key":"2026081812155538400_cit23","doi-asserted-by":"publisher","first-page":"3019","DOI":"10.1021\/ac020361s","article-title":"Strategies for the assessment of\nmatrix effect in quantitative bioanalytical methods based on HPLC-\nMS\/MS","volume":"75","author":"Matuszewski","year":"2003","journal-title":"Anal. Chem."},{"key":"2026081812155538400_cit24","volume-title":"Eurachem Guide: The Fitness\nfor Purpose of Analytical Methods: A Laboratory Guide to Method Validation\nand Related Topics","author":"Cantwell","year":"2025","edition":"3"},{"issue":"6","key":"2026081812155538400_cit25","doi-asserted-by":"publisher","first-page":"1136","DOI":"10.1021\/jasms.3c00077","article-title":"Quantitative LC-MS\/MS. 1. Impact of Points across a\nPeak on the Accuracy and Precision of Peak Area Measurements","volume":"34","author":"Zeng","year":"2023","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"2026081812155538400_cit26","doi-asserted-by":"publisher","first-page":"462146","DOI":"10.1016\/j.chroma.2021.462146","article-title":"A method for the analysis of 121\nmulti-class environmental chemicals in urine by high-performance liquid\nchromatography-tandem mass spectrometry","volume":"1646","author":"Zhu","year":"2021","journal-title":"J.\nChromatogr. A"},{"key":"2026081812155538400_cit27","doi-asserted-by":"publisher","first-page":"117506","DOI":"10.1016\/j.envres.2023.117506","article-title":"Concentrations of neonicotinoid\ninsecticides and their metabolites in multiple urine samples collected\nfrom pregnant women in Japan","volume":"240","author":"Suwannarin","year":"2024","journal-title":"Environ. Res."},{"key":"2026081812155538400_cit28","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1186\/s12940-017-0255-z","article-title":"Distributions\nand determinants of urinary biomarkers of organophosphate pesticide\nexposure in a prospective Spanish birth cohort study","volume":"16","author":"Llop","year":"2017","journal-title":"Environ. Health"},{"key":"2026081812155538400_cit29","unstructured":"Nguyen, V.; Middleton, L. Y. M.; Huang, L.; Zhao, N.; Verly, E.; Kvasnicka, J.; Zimmerman, S.; Sagers, L.; Patel, C. J.; Colacino, J.; Jolliet, O.\n          NHANES 1988\u20132018\n[Data set], Kaggle, 2025."},{"issue":"1","key":"2026081812155538400_cit30","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1016\/j.fct.2010.10.007","article-title":"Assessment of deoxynivalenol metabolite profiles in\nUK adults","volume":"49","author":"Turner","year":"2011","journal-title":"Food Chem. Toxicol."},{"issue":"1","key":"2026081812155538400_cit31","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.toxlet.2013.04.012","article-title":"New insights into the human metabolism\nof the Fusarium mycotoxins\ndeoxynivalenol and zearalenone","volume":"220","author":"Warth","year":"2013","journal-title":"Toxicol. Lett."},{"key":"2026081812155538400_cit32","doi-asserted-by":"publisher","first-page":"114173","DOI":"10.1016\/j.fct.2023.114173","article-title":"The Austrian children\u2019s biomonitoring\nsurvey 2020 part B: Mycotoxins, phytotoxins, phytoestrogens and food\nprocessing contaminants","volume":"182","author":"Ayeni","year":"2023","journal-title":"Food Chem. Toxicol."},{"issue":"21","key":"2026081812155538400_cit33","doi-asserted-by":"publisher","first-page":"11505","DOI":"10.1021\/acs.analchem.7b02759","article-title":"Exposome-scale investigations\nguided by global metabolomics, pathway analysis, and cognitive computing","volume":"89","author":"Warth","year":"2017","journal-title":"Anal. Chem."},{"key":"2026081812155538400_cit34","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1038\/s41370-024-00704-8","article-title":"Associations of exposure\nto bisphenol-A or parabens with markers of liver injury\/function among\nUS adults in NHANES 2011\u20132016","volume":"35","author":"Luo","year":"2025","journal-title":"J. Expo.\nSc. Environm. Epidemiol."}],"container-title":["Environmental Science &amp;\nTechnology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.est.5c04458","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/esthag\/article-pdf\/59\/41\/21818\/41035037\/es5c04458.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/esthag\/article-pdf\/59\/41\/21818\/41035037\/es5c04458.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T18:23:40Z","timestamp":1787077420000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/esthag\/article\/59\/41\/21818\/3670001\/Quantitative-Exposomics-Targeting-over-200"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,10]]},"references-count":34,"journal-issue":{"issue":"41","published-online":{"date-parts":[[2025,10,10]]},"published-print":{"date-parts":[[2025,10,21]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.est.5c04458","relation":{},"ISSN":["0013-936X","1520-5851"],"issn-type":[{"value":"0013-936X","type":"print"},{"value":"1520-5851","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,10]]}}}