{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T15:00:30Z","timestamp":1791385230756,"version":"4.3.3"},"reference-count":36,"publisher":"American Chemical Society (ACS)","issue":"10","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004225","name":"Petrobras","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004225","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Stable carbon isotope ratio measurements (\u03b413C) are traditionally performed by isotope ratio mass spectrometry (IRMS), but recent advances in high-resolution Orbitrap mass spectrometry (Orbitrap MS) enable molecular-level isotope ratio analyses without conversion to simple gases. Here, we systematically evaluate and compare three sample-introduction strategies for Orbitrap-MS-based \u03b413C determination of benzoic acid\u2500dual-inlet (DI), single-inlet (SI), and automated HPLC flow-injection (column-free mode)\u2500assessing how each governs measurement accuracy and precision. Analyses were performed using paired injections of an isotopically certified benzoic acid reference (IAEA-601) and a benzoic acid sample previously characterized by elemental analysis\u2013IRMS (EA-IRMS), following a seven-block bracketing sequence (Ref-Smp-Ref-Smp-Ref-Smp-Ref) to minimize temporal drift and to generate within-run triplicates. Across all configurations, high analytical precision was achieved, within-block relative standard error (\u03c3RSE) consistently below approximately 0.6\u2030. Under DI conditions, replicate means closely approached the EA-IRMS benchmark (\u221227.77\u2030), with residuals of \u22120.40 to +0.50\u2030 on the Exploris 240 and \u22120.58 to \u22122.73\u2030 on the Q Exactive. SI analysis enabled the acquisition of a higher number of individual scans per block, contributing to lower \u03c3RSE (approximately 0.50\u20130.65\u2030) but exhibited larger accuracy offsets (residuals up to approximately 1\u20133\u2030), indicating greater susceptibility to systematic bias. Automated HPLC injection on the Exploris 240, optimized for concentration and AGC (50 \u03bcmol L\u20131 and 2.5 \u00d7 105, respectively), delivered \u03b413C values of 28.1\u2030, \u221227.19\u2030, and \u221227.79\u2030 (residuals of approximately 0.20\u20130.45\u2030) with no significant differences among replicate means (ANOVA\/Tukey, 95% confidence level). Collectively, these findings confirm Orbitrap-MS as a reliable alternative to IRMS for \u03b413C analysis of benzoic acid, and reveal that the choice of injection strategy is the primary determinant of the accuracy\u2013precision\u2013throughput balance achievable with this platform.<\/jats:p>","DOI":"10.1021\/jasms.6c00221","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T10:01:30Z","timestamp":1789120890000},"page":"2472-2482","source":"Crossref","is-referenced-by-count":0,"title":["\u03b413C Determination of Benzoic Acid\nby High-Resolution Orbitrap MS: How Sample Introduction Strategy Governs\nAccuracy and Precision"],"prefix":"10.1021","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9210-870X","authenticated-orcid":true,"given":"Giovanni","family":"B. Bevilaqua","sequence":"first","affiliation":[{"name":"Federal University of Goia\u0301s , , ,","place":["Goia\u0302nia, Brazil, 74690-900"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo G.","family":"Machado","sequence":"additional","affiliation":[{"name":"Federal University of Goia\u0301s , , ,","place":["Goia\u0302nia, Brazil, 74690-900"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1157-6609","authenticated-orcid":true,"given":"Ju\u0301lio C. O.","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Federal University of Goia\u0301s , , ,","place":["Goia\u0302nia, Brazil, 74690-900"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9669-0306","authenticated-orcid":true,"given":"Nerilson Marques","family":"Lima","sequence":"additional","affiliation":[{"name":"Universidade Federal de Alfenas , , , ,","place":["Alfenas, Minas Gerais, Brazil, 37130-001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6257-960X","authenticated-orcid":true,"given":"Alexandre A.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"PETROBRAS Research and Development Center (CENPES), PETROBRAS , ,","place":["Rio de Janeiro, Brazil, 21941-915"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ygor S.","family":"Rocha","sequence":"additional","affiliation":[{"name":"PETROBRAS Research and Development Center (CENPES), PETROBRAS , ,","place":["Rio de Janeiro, Brazil, 21941-915"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4155-6238","authenticated-orcid":true,"given":"Gabriel F.","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Federal University of Goia\u0301s , , ,","place":["Goia\u0302nia, Brazil, 74690-900"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1197-4284","authenticated-orcid":true,"given":"Boniek","family":"Gontijo","sequence":"additional","affiliation":[{"name":"Federal University of Goia\u0301s , , ,","place":["Goia\u0302nia, Brazil, 74690-900"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"issue":"16","key":"2026100710065279700_cit1","doi-asserted-by":"publisher","first-page":"6636","DOI":"10.1021\/acs.est.2c08028","article-title":"Zinc Stable\nIsotope Fractionation Mechanisms during Adsorption on and Substitution\nin Iron (Hydr)Oxides","volume":"57","author":"Yan","year":"2023","journal-title":"Environ. Sci. Technol."},{"key":"2026100710065279700_cit2","doi-asserted-by":"publisher","first-page":"136923","DOI":"10.1016\/j.chemosphere.2022.136923","article-title":"Carbon\nand Hydrogen Stable Isotope Fractionation of Sulfamethoxazole during\nAnaerobic Transformation Catalyzed by Desulfovibrio Vulgaris Hildenborough","volume":"311","author":"Ouyang","year":"2023","journal-title":"Chemosphere"},{"issue":"1","key":"2026100710065279700_cit3","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1038\/s43247-024-01873-y","article-title":"Isotopic\nEvidence for Preferential\nTransport of Fertilizer Nitrogen into the Northern Gulf of Mexico\nduring High Water Discharge","volume":"5","author":"Chen","year":"2024","journal-title":"Commun. Earth Environ."},{"key":"2026100710065279700_cit4","doi-asserted-by":"publisher","first-page":"1440064","DOI":"10.3389\/feart.2024.1440064","article-title":"Tree-Ring\n\u03b4 18O and \u03b4 2H Stable Isotopes Reflect the Global Meteoric\nWater Line","volume":"12","author":"Arosio","year":"2024","journal-title":"Front. Earth Sci. (Lausanne)."},{"key":"2026100710065279700_cit5","doi-asserted-by":"publisher","first-page":"135791","DOI":"10.1016\/j.foodchem.2023.135791","article-title":"A Review of Recent Compound-Specific\nIsotope Analysis\nStudies Applied to Food Authentication","volume":"415","author":"Liu","year":"2023","journal-title":"Food\nChem."},{"key":"2026100710065279700_cit6","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1016\/bs.mie.2017.07.013","article-title":"Applications of Isotope\nRatio Mass Spectrometry in\nSports Drug Testing Accounting for Isotope Fractionation in Analysis\nof Biological Samples","volume":"596","author":"Piper","year":"2017","journal-title":"Methods Enzymol."},{"issue":"16","key":"2026100710065279700_cit7","doi-asserted-by":"publisher","first-page":"4159","DOI":"10.3390\/en17164159","article-title":"Dual Effect\nof Hydrothermal Fluid on Shale Oil Reservoir in Gulong Sag, Songliao\nBasin: Constrained by C-O Isotope and Geochemistry","volume":"17","author":"Li","year":"2024","journal-title":"Energies (Basel)"},{"issue":"1","key":"2026100710065279700_cit8","doi-asserted-by":"publisher","DOI":"10.1007\/s11676-023-01668-5","article-title":"Rising Utilization of Stable\nIsotopes\nin Tree Rings for Climate Change and Forest Ecology","volume":"35","author":"Huang","year":"2024","journal-title":"J. For. Res. (Harbin, China)"},{"key":"2026100710065279700_cit9","doi-asserted-by":"publisher","first-page":"1530","DOI":"10.1021\/ac960935r","article-title":"High-Precision \u03b4 2H and \u03b4 18O Measurement for Water and Volatile Organic Compounds by\nContinuous-Flow Pyrolysis Isotope Ratio Mass Spectrometry","volume":"69","author":"Begley","year":"1997","journal-title":"Anal. Chem."},{"issue":"2","key":"2026100710065279700_cit10","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1080\/10256010902869113","article-title":"Stable\nIsotope Quality Assurance Using the \u201cCalibrated IRMS\u201d\nStrategy","volume":"45","author":"Meijer","year":"2009","journal-title":"Isotopes Environ. Health Stud."},{"issue":"3\u20134","key":"2026100710065279700_cit11","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1016\/j.svgl.2007.08.020","article-title":"Clumped-Isotope\nGeochemistry-The Study of Naturally-Occurring, Multiply-Substituted\nIsotopologues","volume":"262","author":"Eiler","year":"2007","journal-title":"Earth Planet. Sci. Lett."},{"key":"2026100710065279700_cit12","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.1073\/pnas.94.4.1049","article-title":"High-Precision Position-Specific\nIsotope Analysis","volume":"94","author":"Corso","year":"1997","journal-title":"Proc Natl Acad Sci U S A."},{"key":"2026100710065279700_cit13","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1016\/j.ijms.2017.10.002","article-title":"Analysis of\nMolecular Isotopic Structures at High Precision and Accuracy by Orbitrap\nMass Spectrometry","volume":"422","author":"Eiler","year":"2017","journal-title":"Int. J. Mass Spectrom."},{"key":"2026100710065279700_cit14","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.ijms.2012.06.009","article-title":"Orbitrap Mass Spectrometry\nwith Resolving Powers above 1,000,000","volume":"325\u2013327","author":"Denisov","year":"2012","journal-title":"Int.\nJ. Mass Spectrom."},{"issue":"8","key":"2026100710065279700_cit15","doi-asserted-by":"publisher","first-page":"2435","DOI":"10.1038\/s41596-024-00981-5","article-title":"A Guide to\nPrecise Measurements of Isotope Abundance\nby ESI-Orbitrap MS","volume":"19","author":"Kantnerova\u0301","year":"2024","journal-title":"Nat. Protoc."},{"issue":"4","key":"2026100710065279700_cit16","doi-asserted-by":"publisher","first-page":"3077","DOI":"10.1021\/acs.analchem.9b04486","article-title":"Stable Isotope Analysis\nof Intact\nOxyanions Using Electrospray Quadrupole-Orbitrap Mass Spectrometry","volume":"92","author":"Neubauer","year":"2020","journal-title":"Anal. 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Mass Spectrom."},{"issue":"50","key":"2026100710065279700_cit21","doi-asserted-by":"publisher","first-page":"28028","DOI":"10.1021\/acs.analchem.5c06168","article-title":"Source Fingerprinting of PFOA via\nFull- and Intramolecular Stable Isotope Ratios of Carbon Using Orbitrap-IRMS","volume":"97","author":"Nelson","year":"2025","journal-title":"Anal. Chem."},{"issue":"24","key":"2026100710065279700_cit22","doi-asserted-by":"publisher","DOI":"10.1002\/rcm.10139","article-title":"Stable\nCarbon Isotope\nAnalysis of Perfluorooctanoic Acid (PFOA) by Microflow-High Pressure\nLiquid Chromatography-Orbitrap Mass Spectrometry","volume":"39","author":"Wojtal","year":"2025","journal-title":"Rapid Commun. Mass Spectrom."},{"issue":"5","key":"2026100710065279700_cit23","doi-asserted-by":"publisher","first-page":"1196","DOI":"10.1021\/jasms.5c00444","article-title":"Toward Molecular Forensics of Agrochemicals with Orbitrap\nIRMS: Isotopic Fingerprints of Imidacloprid Sources and Elucidating\nHydrolysis","volume":"37","author":"Niemann","year":"2026","journal-title":"J. Am. Soc. Mass Spectrom."},{"issue":"1","key":"2026100710065279700_cit24","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1021\/acs.analchem.5c05530","article-title":"Coupling Liquid Chromatography\nto\nOrbitrap Isotope Ratio Mass Spectrometry: Overcoming Isotope Effects\nof Chromatography and Amount-Dependency by Peak Homogenization","volume":"98","author":"Canavan","year":"2026","journal-title":"Anal. Chem."},{"issue":"7","key":"2026100710065279700_cit25","doi-asserted-by":"publisher","first-page":"1527","DOI":"10.1021\/jasms.5c00092","article-title":"Advancing Stable Isotope\nAnalysis with Orbitrap-MS for Fatty Acid Methyl Esters and Complex\nLipid Matrices","volume":"36","author":"dos Santos","year":"2025","journal-title":"J. Am. Soc. Mass Spectrom."},{"issue":"3","key":"2026100710065279700_cit26","doi-asserted-by":"publisher","first-page":"1897","DOI":"10.1021\/acs.analchem.7b03983","article-title":"Characterization\nof the Spectral Accuracy of an Orbitrap\nMass Analyzer Using Isotope Ratio Mass Spectrometry","volume":"90","author":"Khodjaniyazova","year":"2018","journal-title":"Anal. Chem."},{"issue":"13","key":"2026100710065279700_cit27","doi-asserted-by":"publisher","first-page":"9764","DOI":"10.1021\/acs.analchem.5c07111","article-title":"Lessons Learned in Orbitrap MS-Based\nIsotope Ratio Analysis of Organic Acid Mixtures","volume":"98","author":"Machado","year":"2026","journal-title":"Anal. Chem."},{"key":"2026100710065279700_cit28","doi-asserted-by":"publisher","first-page":"117084","DOI":"10.1016\/j.ijms.2023.117084","article-title":"Accuracy and Precision of ESI-Orbitrap-IRMS\nObservations of Hours to Tens of Hours via Reservoir Injection","volume":"490","author":"Csernica","year":"2023","journal-title":"Int. J. Mass Spectrom."},{"issue":"2","key":"2026100710065279700_cit29","doi-asserted-by":"publisher","first-page":"1092","DOI":"10.1021\/acs.analchem.1c04141","article-title":"Simultaneous,\nHigh-Precision Measurements of \u03b4 2H and \u03b4 13C in Nanomole Quantities of Acetate Using Electrospray Ionization-Quadrupole-Orbitrap\nMass Spectrometry","volume":"94","author":"Mueller","year":"2022","journal-title":"Anal. Chem."},{"key":"2026100710065279700_cit30","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.supflu.2012.10.014","article-title":"Supercritical\nCO2 Extraction of Phthalic Anhydride, Benzoic Acid and Maleic Acid\nfrom Petrochemical Wastes","volume":"74","author":"Kamali","year":"2013","journal-title":"J. Supercrit. Fluids"},{"issue":"7","key":"2026100710065279700_cit31","doi-asserted-by":"publisher","first-page":"5391","DOI":"10.1021\/acs.energyfuels.6b00448","article-title":"Removal\nof Benzoic Acid in Heavy\nOils by Esterification Using Modified Ferrierite: Roles of Br\u00f8nsted\nand Lewis Acid Sites","volume":"30","author":"Lee","year":"2016","journal-title":"Energy Fuels"},{"key":"2026100710065279700_cit32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2019\/5721585","article-title":"Benzoic Acid\nUsed as Food and Feed Additives Can Regulate Gut Functions","volume":"2019","author":"Mao","year":"2019","journal-title":"BioMed. Research International. Hindawi Limited"},{"issue":"14","key":"2026100710065279700_cit33","doi-asserted-by":"publisher","first-page":"3084","DOI":"10.1080\/10408398.2015.1087964","article-title":"Benzoic Acid and Its Derivatives\nas Naturally Occurring Compounds in Foods and as Additives: Uses,\nExposure, and Controversy","volume":"57","author":"del Olmo","year":"2017","journal-title":"Crit. Rev. Food Sci.\nNutr."},{"issue":"4","key":"2026100710065279700_cit34","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1111\/2041-210X.12165","article-title":"Comparison of Methods for Stable\nIsotope Ratio (\u03b413C, \u03b415N, \u03b42H, \u03b418O) Measurements of Feathers","volume":"5","author":"Bontempo","year":"2014","journal-title":"Methods Ecol. Evol."},{"issue":"18","key":"2026100710065279700_cit35","doi-asserted-by":"publisher","DOI":"10.1002\/rcm.9347","article-title":"Position-Specific Carbon Isotope\nAnalysis of Serine by Gas Chromatography\/Orbitrap Mass Spectrometry,\nand an Application to Plant Metabolism","volume":"36","author":"Wilkes","year":"2022","journal-title":"Rapid\nCommun. Mass Spectrom."},{"issue":"41","key":"2026100710065279700_cit36","doi-asserted-by":"publisher","first-page":"22777","DOI":"10.1021\/acs.analchem.5c04367","article-title":"Oxygen Isotope Analyses of Phosphate and Organophosphorus\nCompounds by Electrospray Ionization Orbitrap Mass Spectrometry","volume":"97","author":"Bernet","year":"2025","journal-title":"Anal. Chem."}],"container-title":["Journal of the American\nSociety for Mass Spectrometry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/jasms.6c00221","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jamsef\/article-pdf\/37\/10\/2472\/68480677\/jasms.6c00221.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jamsef\/article-pdf\/37\/10\/2472\/68480677\/jasms.6c00221.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T14:31:23Z","timestamp":1791383483000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jamsef\/article\/37\/10\/2472\/5428186\/13C-Determination-of-Benzoic-Acid-by-High"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,11]]},"references-count":36,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,9,11]]},"published-print":{"date-parts":[[2026,10,7]]}},"URL":"https:\/\/doi.org\/10.1021\/jasms.6c00221","relation":{},"ISSN":["1044-0305","1879-1123"],"issn-type":[{"value":"1044-0305","type":"print"},{"value":"1879-1123","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,11]]}}}