{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T12:48:27Z","timestamp":1785847707142,"version":"3.56.0"},"reference-count":33,"publisher":"American Chemical Society (ACS)","issue":"30","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UG3 TR004139"],"award-info":[{"award-number":["UG3 TR004139"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30 CA 023168"],"award-info":[{"award-number":["P30 CA 023168"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA282451"],"award-info":[{"award-number":["R01CA282451"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA284268"],"award-info":[{"award-number":["R01CA284268"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS129671"],"award-info":[{"award-number":["R01NS129671"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006827","name":"Florida Department of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006827","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000871","name":"Mayo Clinic","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Waters Scientific Corporation","award":["40002775"],"award-info":[{"award-number":["40002775"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The mutation status of isocitrate dehydrogenase (IDH) in glioma patients has diagnostic and prognostic significance but is available only after surgery. Rapid and sensitive intraoperative molecular diagnosis is essential for distinguishing tumor from infiltrative and from normal brain tissue to maximize safe resection. IDH-mutant (mut)tumors produce high concentrations of 2-hydroxyglutarate (2HG), which serves as a surrogate marker of IDH mutation. Here, we use desorption electrospray ionization-multiple reaction monitoring (DESI-MRM), a form of mass spectrometry (MS), for rapid prediction of IDH mutation status. A set of 30 human brain smears was analyzed using DESI-MRM experiments to predict the mutation status of IDH and quantify 2HG in glioma samples within 2 min (endogenous reference molecule) or 7 min (external standard). Nanoelectrospray ionization (nESI) was employed as a validation method. An isotopically labeled surrogate internal standard allowed quantitative measurement of 2HG and clear separation between IDH-mut and IDH-wildtype (wt) samples, showing 100% agreement with clinical diagnosis. 2HG concentrations in IDH-mut samples ranged from 88 to 1445 ng mg\u20131, while IDH-wt samples exhibited 2HG concentrations of 9\u201315 ng mg\u20131. Calibration curves showed method accuracy within \u226415%. The quantitative results obtained using isotopically labeled standards showed a strong correlation between IDH mutation score and 2HG concentrations, as did an earlier semiquantitative (ratiometric, endogenous standard) method. These findings highlight the standalone capability of DESI-MRM for making measurements to justify assessments for intraoperative diagnosis and to support surgical decision-making to improve patient outcomes.<\/jats:p>","DOI":"10.1021\/acs.analchem.6c00520","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T04:15:12Z","timestamp":1784607312000},"page":"22080-22087","source":"Crossref","is-referenced-by-count":0,"title":["Isocitrate\nDehydrogenase Mutation Assessment in Human\nGlioma Using Desorption Electrospray Ionization\u2013Multiple Reaction\nMonitoring"],"prefix":"10.1021","volume":"98","author":[{"given":"Mahdiyeh","family":"Shahi","sequence":"first","affiliation":[{"name":"Purdue University , , , ,","place":["West Lafayette, Indiana, United States, 47907"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diogo Moniz","family":"Garcia","sequence":"additional","affiliation":[{"name":"Washington University in St. Louis , , , ,","place":["St. Louis, Missouri, United States, 63110"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Quin\u0303ones-Hinojosa","sequence":"additional","affiliation":[{"name":"Mayo Clinic , , , ,","place":["Jacksonville, Florida, United States, 32224"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9581-9603","authenticated-orcid":true,"given":"R. Graham","family":"Cooks","sequence":"additional","affiliation":[{"name":"Purdue University , , , ,","place":["West Lafayette, Indiana, United States, 47907"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"issue":"8","key":"2026080408073352300_cit1","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1093\/neuonc\/noab106","article-title":"The 2021 WHO Classification of Tumors of the Central\nNervous System: A Summary","volume":"23","author":"Louis","year":"2021","journal-title":"Neuro-Oncology"},{"issue":"1","key":"2026080408073352300_cit2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3171\/2020.10.JNS203366","article-title":"Influence of Supramarginal Resection on Survival Outcomes\nafter Gross-Total Resection of IDH\u2013Wild-Type Glioblastoma","volume":"136","author":"Vivas-Buitrago","year":"2022","journal-title":"J. Neurosurg."},{"issue":"1","key":"2026080408073352300_cit3","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1007\/s11060-017-2564-z","article-title":"Treatment Outcome\nof Patients with Recurrent Glioblastoma Multiforme: A Retrospective\nMulticenter Analysis","volume":"135","author":"Van Linde","year":"2017","journal-title":"J. Neurooncol."},{"issue":"3","key":"2026080408073352300_cit4","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1158\/2767-9764.CRC-23-0271","article-title":"D-2-HG Inhibits IDH1mut Glioma Growth via FTO Inhibition and Resultant m6A Hypermethylation","volume":"4","author":"Pianka","year":"2024","journal-title":"Cancer Res. Commun."},{"issue":"2","key":"2026080408073352300_cit5","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.trecan.2017.12.005","article-title":"Metabolism,\nActivity, and Targeting\nof D- and L-2-Hydroxyglutarates","volume":"4","author":"Ye","year":"2018","journal-title":"Trends Cancer"},{"issue":"9","key":"2026080408073352300_cit6","doi-asserted-by":"publisher","DOI":"10.3390\/cells10092345","article-title":"D-2-Hydroxyglutarate in Glioma Biology","volume":"10","author":"Chou","year":"2021","journal-title":"Cells"},{"issue":"1","key":"2026080408073352300_cit7","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1158\/0008-5472.CAN-15-0934","article-title":"Noninvasive Quantification of 2-Hydroxyglutarate in\nHuman Gliomas with IDH1 and IDH2Mutations","volume":"76","author":"Emir","year":"2016","journal-title":"Cancer\nRes."},{"issue":"23","key":"2026080408073352300_cit8","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2318843121","article-title":"Rapid Detection of IDH Mutations\nin Gliomas by Intraoperative Mass Spectrometry","volume":"121","author":"Hua","year":"2024","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"issue":"1","key":"2026080408073352300_cit9","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-77044-y","article-title":"Detection\nof IDH Mutation in Glioma by Desorption Electrospray\nIonization (DESI) Tandem Mass Spectrometry","volume":"14","author":"Shahi","year":"2024","journal-title":"Sci. Rep."},{"issue":"7274","key":"2026080408073352300_cit10","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1038\/nature08617","article-title":"Cancer-Associated IDH1Mutations Produce 2-Hydroxyglutarate","volume":"462","author":"Dang","year":"2009","journal-title":"Nature"},{"key":"2026080408073352300_cit11","unstructured":"A Phase I\/II Study of Zotiraciclib for Recurrent\nMalignant Gliomas\nWith Isocitrate Dehydrogenase 1 or 2 (IDH1 or IDH2) Mutations\n          2022\n          https:\/\/clinicaltrials.gov\/study\/NCT05588141 (accessed May 16, 2023)."},{"issue":"7","key":"2026080408073352300_cit12","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1056\/NEJMoa2304194","article-title":"Vorasidenib\nin IDH1- or IDH2-Mutant Low-Grade Glioma","volume":"389","author":"Mellinghoff","year":"2023","journal-title":"N.\nEng.l J. Med."},{"key":"2026080408073352300_cit13","doi-asserted-by":"publisher","DOI":"10.1016\/j.saa.2024.125063","article-title":"Study of the Relationship\namong Biomarkers, Cell and Tissue of Glioma through Raman Spectroscopy","volume":"325","author":"Ge","year":"2025","journal-title":"Spectrochim,. Acta, Part A"},{"issue":"5","key":"2026080408073352300_cit14","doi-asserted-by":"publisher","DOI":"10.3390\/cancers17050734","article-title":"Fluorescence-Guided\nResection of GL261 Red-FLuc and TRP-mCherry-FLuc Mouse Glioblastoma\nTumors","volume":"17","author":"Rodgers","year":"2025","journal-title":"Cancers"},{"issue":"1","key":"2026080408073352300_cit15","doi-asserted-by":"publisher","DOI":"10.1038\/s41523-021-00318-5","article-title":"Interim Clinical\nTrial Analysis of Intraoperative Mass Spectrometry for Breast Cancer\nSurgery","volume":"7","author":"Basu","year":"2021","journal-title":"npj Breast Cancer"},{"issue":"8052","key":"2026080408073352300_cit16","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1038\/s41586-025-08584-0","article-title":"Mass-Spectrometry-Based\nProteomics:\nFrom Single Cells to Clinical Applications","volume":"638","author":"Guo","year":"2025","journal-title":"Nature"},{"issue":"5","key":"2026080408073352300_cit17","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1002\/mas.21664","article-title":"Mass Spectrometry\nTechnologies to Advance Care for Cancer Patients in Clinical and Intraoperative\nUse","volume":"40","author":"Zhang","year":"2021","journal-title":"Mass Spectrom. Rev."},{"issue":"5695","key":"2026080408073352300_cit18","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1126\/science.1104404","article-title":"Mass Spectrometry\nSampling Under Ambient Conditions with Desorption Electrospray Ionization","volume":"306","author":"Taka\u0301ts","year":"2004","journal-title":"Science"},{"issue":"19","key":"2026080408073352300_cit19","doi-asserted-by":"publisher","first-page":"6939","DOI":"10.1021\/acs.analchem.1c03583","article-title":"Evaluation of the Sensitivity\nof Metabolic Profiling by Rapid Evaporative Ionization Mass Spectrometry:\nToward More Radical Oral Cavity Cancer Resections","volume":"94","author":"Vaysse","year":"2022","journal-title":"Anal. Chem."},{"issue":"28","key":"2026080408073352300_cit20","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2104411118","article-title":"Rapid Diagnosis\nand Tumor Margin Assessment during Pancreatic Cancer Surgery with\nthe MasSpec Pen Technology","volume":"118","author":"King","year":"2021","journal-title":"Proc. Natl. Acad.\nSci. U.S.A."},{"issue":"21","key":"2026080408073352300_cit21","doi-asserted-by":"publisher","first-page":"4058","DOI":"10.1039\/C7AN01334E","article-title":"Analysis of Human Gliomas by Swab\nTouch Spray-Mass Spectrometry: Applications to Intraoperative Assessment\nof Surgical Margins and Presence of Oncometabolites","volume":"142","author":"Pirro","year":"2017","journal-title":"Analyst"},{"issue":"3","key":"2026080408073352300_cit22","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1021\/acs.analchem.3c03156","article-title":"Lipidomic-Based\nApproach to 10 s Classification of Major Pediatric Brain Cancer Types\nwith Picosecond Infrared Laser Mass Spectrometry","volume":"96","author":"Woolman","year":"2024","journal-title":"Anal. Chem."},{"issue":"20","key":"2026080408073352300_cit23","doi-asserted-by":"publisher","first-page":"7729","DOI":"10.1021\/ac201251s","article-title":"Real Time\nAnalysis of Brain Tissue by Direct Combination of Ultrasonic Surgical\nAspiration and Sonic Spray Mass Spectrometry","volume":"83","author":"Scha\u0308fer","year":"2011","journal-title":"Anal. Chem."},{"key":"2026080408073352300_cit24","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.jmsacl.2025.10.002","article-title":"Ambient Ionization Mass Spectrometry in Brain Cancer\nDiagnosis","volume":"38","author":"Shahi","year":"2025","journal-title":"J. Mass Spectrom. Adv. Clin. Lab"},{"issue":"11","key":"2026080408073352300_cit25","doi-asserted-by":"publisher","first-page":"2827","DOI":"10.1039\/C4MB00250D","article-title":"Structural Mass\nSpectrometry of Tissue Extracts to Distinguish Cancerous and Non-Cancerous\nBreast Diseases","volume":"10","author":"Hines","year":"2014","journal-title":"Mol. BioSyst."},{"issue":"14","key":"2026080408073352300_cit26","doi-asserted-by":"publisher","first-page":"2017","DOI":"10.1021\/ac50036a020","article-title":"Multiple Reaction Monitoring in Mass\nSpectrometry\/Mass Spectrometry for Direct Analysis of Complex Mixtures","volume":"50","author":"Kondrat","year":"1978","journal-title":"Anal. Chem."},{"issue":"22","key":"2026080408073352300_cit27","doi-asserted-by":"publisher","first-page":"2359","DOI":"10.1021\/j100511a002","article-title":"Chlorine\nIsotope Effects in Mass\nSpectrometry by Multiple Reaction Monitoring","volume":"82","author":"Zakett","year":"1978","journal-title":"J. Phys. Chem. A"},{"issue":"22","key":"2026080408073352300_cit28","doi-asserted-by":"publisher","first-page":"5438","DOI":"10.1039\/C8AN01661E","article-title":"Logical MS\/MS Scans:\nA New Set of Operations for Tandem Mass Spectrometry","volume":"143","author":"Snyder","year":"2018","journal-title":"Analyst"},{"issue":"30","key":"2026080408073352300_cit29","doi-asserted-by":"publisher","first-page":"7929","DOI":"10.1007\/s00216-019-02198-y","article-title":"Intraoperative Detection\nof Isocitrate Dehydrogenase Mutations in Human Gliomas Using a Miniature\nMass Spectrometer","volume":"411","author":"Brown","year":"2019","journal-title":"Anal. Bioanal. Chem."},{"issue":"4","key":"2026080408073352300_cit30","doi-asserted-by":"publisher","first-page":"902","DOI":"10.1093\/jalm\/jfaa233","article-title":"Intraoperative Mass Spectrometry\nPlatform for IDH Mutation Status Prediction, Glioma Diagnosis, and\nEstimation of Tumor Cell Infiltration","volume":"6","author":"Brown","year":"2021","journal-title":"J. Appl.\nLab. Med."},{"issue":"8","key":"2026080408073352300_cit31","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1139\/y59-099","article-title":"A Rapid Method of Total Lipid Extraction and Purification","volume":"37","author":"Bligh","year":"1959","journal-title":"Can. J. Biochem. Physiol."},{"issue":"5","key":"2026080408073352300_cit32","doi-asserted-by":"publisher","DOI":"10.1002\/cnr2.1799","article-title":"Association between Altered Metabolism and Genetic\nMutations in Human Glioma","volume":"6","author":"Pearl","year":"2023","journal-title":"Cancer Rep."},{"key":"2026080408073352300_cit33","unstructured":"Shahi M.; Cooks R. G. Desorption Electrospray Ionization Mass Spectrometry for Quantitative and Semiquantitative Assessment of 2-Hydroxyglutarate; Purdue University, 2024."}],"container-title":["Analytical Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.analchem.6c00520","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/ancham\/article-pdf\/98\/30\/22080\/66069834\/acs.analchem.6c00520.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/ancham\/article-pdf\/98\/30\/22080\/66069834\/acs.analchem.6c00520.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T12:27:09Z","timestamp":1785846429000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/ancham\/article\/98\/30\/22080\/5222708\/Isocitrate-Dehydrogenase-Mutation-Assessment-in"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,21]]},"references-count":33,"journal-issue":{"issue":"30","published-online":{"date-parts":[[2026,7,21]]},"published-print":{"date-parts":[[2026,8,4]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.analchem.6c00520","relation":{},"ISSN":["0003-2700","1520-6882"],"issn-type":[{"value":"0003-2700","type":"print"},{"value":"1520-6882","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,21]]}}}