{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T05:54:07Z","timestamp":1793771647410,"version":"4.6.1"},"reference-count":35,"publisher":"IOP Publishing","issue":"3","license":[{"start":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T00:00:00Z","timestamp":1745366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T00:00:00Z","timestamp":1745366400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/iopscience.iop.org\/info\/page\/text-and-data-mining"}],"funder":[{"name":"Heidi Ras Foundation","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]},{"DOI":"10.13039\/501100022575","name":"Agroscope","doi-asserted-by":"crossref","award":["15668"],"award-info":[{"award-number":["15668"]}],"id":[{"id":"10.13039\/501100022575","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["iopscience.iop.org"],"crossmark-restriction":false},"short-container-title":["J. Breath Res."],"published-print":{"date-parts":[[2025,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The identification and quantitation of volatile organic compounds (VOCs) in exhaled human breath has attracted considerable interest due to its potential application in medical diagnostics, environmental exposure assessment, and forensic applications. Secondary electrospray ionization-mass spectrometry (SESI-MS) is a method capable of detecting thousands of VOCs. Nevertheless, most studies using SESI-MS for breath analysis have relied primarily on MS<jats:sup>1<\/jats:sup> measurements for identifications and quantification, which are susceptible to misassignments and errors. In this study, we targeted several endogenous compounds (C5 to C10 aldehydes, limonene and pyridine), known to occur in breath. These compounds were measured and quantified in exhaled breath from 12 volunteers over several days using three different acquisition methods: full scan, targeted selected ion monitoring and parallel reaction monitoring. These methods were used for identification and quantification by comparing with measurements of external standards. High-abundance features such as limonene and pyridine were successfully identified and quantified in exhaled human breath with all three methods, with MS<jats:sup>2<\/jats:sup> measurements supporting identification, albeit with limitations to separate between limonene and <jats:italic>\u03b1<\/jats:italic>-\/<jats:italic>\u03b2<\/jats:italic>-pinene. For low-abundance features, the study highlights the challenges of false assignments in SESI-MS, even with MS<jats:sup>2<\/jats:sup> measurements. This was demonstrated in the case of aldehydes, which could not be reliably separated from isomeric ketones present in breath, leading to incorrect quantification.<\/jats:p>","DOI":"10.1088\/1752-7163\/adc9da","type":"journal-article","created":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T22:51:08Z","timestamp":1744066268000},"page":"036002","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Challenges in the identification and quantitation in on-line breath analysis"],"prefix":"10.1088","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-4056-9159","authenticated-orcid":true,"given":"Timon","family":"K\u00e4ser","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5066-533X","authenticated-orcid":true,"given":"Stamatios","family":"Giannoukos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5211-4358","authenticated-orcid":true,"given":"Renato","family":"Zenobi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"266","published-online":{"date-parts":[[2025,4,23]]},"reference":[{"key":"jbradc9dabib1","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1039\/9781839166990-00323","article-title":"Monitoring drug pharmacokinetics","author":"Schmidt","year":"2022"},{"key":"jbradc9dabib2","doi-asserted-by":"publisher","DOI":"10.1016\/j.trac.2023.117320","article-title":"Mass spectrometric analysis of exhaled breath: recent advances and future perspectives","volume":"168","author":"Hu","year":"2023","journal-title":"TRAC Trends Anal. Chem."},{"key":"jbradc9dabib3","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1039\/d2ay01778d","article-title":"Analysis of volatile short-chain fatty acids in the gas phase using secondary electrospray ionization coupled to mass spectrometry","volume":"15","author":"W\u00fcthrich","year":"2022","journal-title":"Anal. Methods"},{"key":"jbradc9dabib4","doi-asserted-by":"publisher","DOI":"10.1016\/j.aca.2021.338876","article-title":"Quantification of volatile organic compounds by secondary electrospray ionization-high resolution mass spectrometry","volume":"1180","author":"Liu","year":"2021","journal-title":"Anal. Chim. Acta"},{"key":"jbradc9dabib5","doi-asserted-by":"publisher","first-page":"10803","DOI":"10.1021\/acs.chemrev.9b00005","article-title":"On-line analysis of exhaled breath","volume":"119","author":"Bruderer","year":"2019","journal-title":"Chem. Rev."},{"key":"jbradc9dabib6","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1021\/ac5035874","article-title":"Direct quantification of chemical warfare agents and related compounds at low ppt levels: comparing active capillary dielectric barrier discharge plasma ionization and secondary electrospray ionization mass spectrometry","volume":"87","author":"Wolf","year":"2015","journal-title":"Anal. Chem."},{"key":"jbradc9dabib7","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/j.jasms.2008.10.006","article-title":"Secondary electrospray ionization (SESI) of ambient vapors for explosive detection at concentrations below parts per trillion","volume":"20","author":"Mart\u00ednez-Lozano","year":"2009","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"jbradc9dabib8","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.ijms.2009.04.002","article-title":"Analysis of the isobaric compounds propanol, acetic acid and methyl formate in humid air and breath by selected ion flow tube mass spectrometry, SIFT-MS","volume":"285","author":"Pysanenko","year":"2009","journal-title":"Int. J. Mass Spectrom."},{"key":"jbradc9dabib9","doi-asserted-by":"publisher","DOI":"10.1088\/1752-7163\/ad4736","article-title":"Impact of breath sample collection method and length of storage of breath samples in Tedlar bags on the level of selected volatiles assessed using gas chromatography-ion mobility spectrometry (GC-IMS)","volume":"18","author":"Czippelov\u00e1","year":"2024","journal-title":"J. Breath Res."},{"key":"jbradc9dabib10","doi-asserted-by":"publisher","DOI":"10.3929\/ethz-b-000351718","article-title":"On-line breath metabolomics with ambient high-resolution mass spectrometry","author":"Gaugg","year":"2019"},{"key":"jbradc9dabib11","doi-asserted-by":"publisher","first-page":"1709","DOI":"10.1074\/MCP.O112.019802","article-title":"Targeted proteomic quantification on quadrupole-orbitrap mass spectrometer","volume":"11","author":"Gallien","year":"2012","journal-title":"Mol. Cell. Proteomics"},{"key":"jbradc9dabib12","doi-asserted-by":"publisher","first-page":"2097","DOI":"10.1021\/es5002105","article-title":"Identifying small molecules via high resolution mass spectrometry: communicating confidence","volume":"48","author":"Schymanski","year":"2014","journal-title":"Environ. Sci. Technol."},{"key":"jbradc9dabib13","doi-asserted-by":"publisher","first-page":"5258","DOI":"10.3390\/molecules27165258","article-title":"Exhaled aldehydes as biomarkers for lung diseases: a narrative review","volume":"27","author":"Floss","year":"2022","journal-title":"Molecules"},{"key":"jbradc9dabib14","doi-asserted-by":"publisher","DOI":"10.1016\/j.snb.2019.127371","article-title":"Measurement of temperature and relative humidity in exhaled breath","volume":"304","author":"Mansour","year":"2020","journal-title":"Sens. Actuators B"},{"key":"jbradc9dabib15","doi-asserted-by":"publisher","first-page":"3887","DOI":"10.1021\/ac404175e","article-title":"Dynamic vapor generator that simulates transient odor emissions of victims entrapped in the voids of collapsed buildings","volume":"86","author":"Statheropoulos","year":"2014","journal-title":"Anal. Chem."},{"key":"jbradc9dabib16","doi-asserted-by":"publisher","first-page":"2371","DOI":"10.1007\/s13361-017-1752-6","article-title":"Molecular communication over gas stream channels using portable mass spectrometry","volume":"28","author":"Giannoukos","year":"2017","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"jbradc9dabib17","doi-asserted-by":"publisher","first-page":"10871","DOI":"10.1021\/acs.analchem.4c01924","article-title":"Internal standard addition system for online breath analysis","volume":"96","author":"W\u00fcthrich","year":"2024","journal-title":"Anal. Chem."},{"key":"jbradc9dabib18","doi-asserted-by":"publisher","first-page":"10901","DOI":"10.5194\/ACP-23-10901-2023","article-title":"Compilation of Henry\u2019s law constants (version 5.0.0) for water as solvent","volume":"23","author":"Sander","year":"2023","journal-title":"Atmos. Chem. Phys."},{"key":"jbradc9dabib19","doi-asserted-by":"crossref","first-page":"297","DOI":"10.3891\/acta.chem.scand.30a-0297","article-title":"Theory for the Determination of Vapour Pressures by the Transpiration Method","volume":"30","author":"Kvande","year":"1976","journal-title":"Acta Chem. Scand. A"},{"key":"jbradc9dabib20","doi-asserted-by":"publisher","DOI":"10.1016\/J.IJMS.2022.116892","article-title":"Selected Ion Flow Tube\u2014Mass Spectrometry (SIFT-MS) study of the reactions of H3O+, NO+ and O2+ with a range of oxygenated volatile organic carbons (OVOCs)","volume":"479","author":"Roberts","year":"2022","journal-title":"Int. J. Mass Spectrom."},{"key":"jbradc9dabib21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/rcm.9266","article-title":"Resolving isobaric interferences in direct infusion tandem mass spectrometry","volume":"36","author":"Kaeslin","year":"2022","journal-title":"Rapid Commun. Mass Spectrom."},{"key":"jbradc9dabib22","doi-asserted-by":"publisher","first-page":"2028","DOI":"10.1021\/acs.jproteome.0c00866","article-title":"The rawrr R package: direct access to orbitrap data and beyond","volume":"20","author":"Kockmann","year":"2021","journal-title":"J. Proteome Res."},{"key":"jbradc9dabib23","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1038\/s41592-019-0344-8","article-title":"SIRIUS 4: a rapid tool for turning tandem mass spectra into metabolite structure information","volume":"16","author":"D\u00fchrkop","year":"2019","journal-title":"Nat. Methods"},{"key":"jbradc9dabib24","doi-asserted-by":"publisher","first-page":"12580","DOI":"10.1073\/pnas.1509788112","article-title":"Searching molecular structure databases with tandem mass spectra using CSI:FingerID","volume":"112","author":"D\u00fchrkop","year":"2015","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"jbradc9dabib25","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1038\/s41587-020-0740-8","article-title":"Systematic classification of unknown metabolites using high-resolution fragmentation mass spectra","volume":"39","author":"D\u00fchrkop","year":"2020","journal-title":"Nat. Biotechnol."},{"key":"jbradc9dabib26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13321-016-0174-y","article-title":"ClassyFire: automated chemical classification with a comprehensive, computable taxonomy","volume":"8","author":"Djoumbou Feunang","year":"2016","journal-title":"J. Cheminform."},{"key":"jbradc9dabib27","doi-asserted-by":"publisher","first-page":"2795","DOI":"10.1021\/acs.jnatprod.1c00399","article-title":"NPClassifier: a deep neural network-based structural classification tool for natural products","volume":"84","author":"Kim","year":"2021","journal-title":"J. Nat. Prod."},{"key":"jbradc9dabib28","doi-asserted-by":"publisher","first-page":"2134","DOI":"10.1039\/c3an36756h","article-title":"Blood and breath levels of selected volatile organic compounds in healthy volunteers","volume":"138","author":"Mochalski","year":"2013","journal-title":"Analyst"},{"key":"jbradc9dabib29","doi-asserted-by":"publisher","DOI":"10.1088\/1752-7155\/10\/4\/046010","article-title":"Limonene in exhaled breath is elevated in hepatic encephalopathy","volume":"10","author":"O\u2019Hara","year":"2016","journal-title":"J. Breath Res."},{"key":"jbradc9dabib30","article-title":"Atmospheric measurement techniques MS\/MS studies for the selective detection of isomeric biogenic VOCs using a townsend discharge triple quadrupole tandem MS and a PTR-Linear Ion Trap MS","author":"Uller","year":"2009"},{"key":"jbradc9dabib31","doi-asserted-by":"publisher","first-page":"1967","DOI":"10.1021\/jasms.2c00201","article-title":"How soft is secondary electrospray ionization?","volume":"33","author":"Kaeslin","year":"2022","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"jbradc9dabib32","doi-asserted-by":"publisher","DOI":"10.1088\/1752-7163\/ab9f8b","article-title":"Real-time breath analysis of exhaled compounds upon peppermint oil ingestion by secondary electrospray ionization-high resolution mass spectrometry: technical aspects","volume":"14","author":"Gisler","year":"2020","journal-title":"J. Breath Res."},{"key":"jbradc9dabib33","doi-asserted-by":"publisher","first-page":"127","DOI":"10.2533\/chimia.2022.127","article-title":"Comparison of plasma ionization- and secondary electrospray ionization- high-resolution mass spectrometry for real-time breath analysis","volume":"76","author":"Zeng","year":"2022","journal-title":"Chimia"},{"key":"jbradc9dabib34","doi-asserted-by":"publisher","DOI":"10.1088\/1752-7163\/AB8865","article-title":"Breath carbonyl levels in a human population of seven hundred participants","volume":"14","author":"McCartney","year":"2020","journal-title":"J. Breath Res."},{"key":"jbradc9dabib35","doi-asserted-by":"publisher","first-page":"4344","DOI":"10.1021\/acs.analchem.2c04604","article-title":"Analysis of a broad range of carbonyl metabolites in exhaled breath by UHPLC-MS","volume":"95","author":"Xie","year":"2023","journal-title":"Anal. Chem."}],"container-title":["Journal of Breath Research"],"original-title":[],"link":[{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1752-7163\/adc9da","content-type":"text\/html","content-version":"am","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1752-7163\/adc9da\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1752-7163\/adc9da","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1752-7163\/adc9da\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1752-7163\/adc9da\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1752-7163\/adc9da\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1752-7163\/adc9da\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"similarity-checking"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1752-7163\/adc9da\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T06:09:07Z","timestamp":1745388547000},"score":1,"resource":{"primary":{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1752-7163\/adc9da"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,23]]},"references-count":35,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,4,23]]},"published-print":{"date-parts":[[2025,7,1]]}},"URL":"https:\/\/doi.org\/10.1088\/1752-7163\/adc9da","relation":{},"ISSN":["1752-7155","1752-7163"],"issn-type":[{"value":"1752-7155","type":"print"},{"value":"1752-7163","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,23]]},"assertion":[{"value":"Challenges in the identification and quantitation in on-line breath analysis","name":"article_title","label":"Article Title"},{"value":"Journal of Breath Research","name":"journal_title","label":"Journal Title"},{"value":"paper","name":"article_type","label":"Article Type"},{"value":"\u00a9 2025 The Author(s). Published by IOP Publishing Ltd","name":"copyright_information","label":"Copyright Information"},{"value":"2025-01-10","name":"date_received","label":"Date Received","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2025-04-07","name":"date_accepted","label":"Date Accepted","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2025-04-23","name":"date_epub","label":"Online publication date","group":{"name":"publication_dates","label":"Publication dates"}}]}}