{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T04:29:27Z","timestamp":1772252967277,"version":"3.50.1"},"reference-count":32,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,10,23]],"date-time":"2021-10-23T00:00:00Z","timestamp":1634947200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000181","name":"United States Air Force Office of Scientific Research","doi-asserted-by":"publisher","award":["AFOSR FA9550-12-1-0400"],"award-info":[{"award-number":["AFOSR FA9550-12-1-0400"]}],"id":[{"id":"10.13039\/100000181","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81903575"],"award-info":[{"award-number":["81903575"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Isobaric ions having the same mass-to-charge ratio cannot be separately identified by mass spectrometry (MS) alone, but this limitation can be overcome by using hydrogen\u2013deuterium exchange (HDX) in microdroplets. Because isobaric ions may contain a varied number of exchangeable sites and different types of functional groups, each one produces a unique MS spectral pattern after droplet spray HDX without the need for MS\/MS experiments or introduction of ion mobility measurements. As an example of the power of this approach, isobaric ions in urinary metabolic profiles are identified and used to distinguish between healthy individuals and those having bladder cancer.<\/jats:p>","DOI":"10.3390\/metabo11110728","type":"journal-article","created":{"date-parts":[[2021,10,24]],"date-time":"2021-10-24T22:07:11Z","timestamp":1635113231000},"page":"728","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Distinguishing between Isobaric Ions Using Microdroplet Hydrogen\u2013Deuterium Exchange Mass Spectrometry"],"prefix":"10.3390","volume":"11","author":[{"given":"Xiaowei","family":"Song","sequence":"first","affiliation":[{"name":"Department of Chemistry, Stanford University, Stanford, CA 94305, USA"},{"name":"Department of Chemistry, Fudan University, Shanghai 200438, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Fudan University, Shanghai 200438, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad","family":"Mofidfar","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Stanford University, Stanford, CA 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5266-4253","authenticated-orcid":false,"given":"Richard N.","family":"Zare","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Stanford University, Stanford, CA 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4266","DOI":"10.1021\/acs.analchem.9b00807","article-title":"Ambient Ionization Mass Spectrometry: Recent Developments and Applications","volume":"91","author":"Feider","year":"2019","journal-title":"Anal. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1126\/science.1104404","article-title":"Mass Spectrometry Sampling Under Ambient Conditions with Desorption Electrospray Ionization","volume":"306","author":"Takats","year":"2004","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2226","DOI":"10.1021\/jasms.0c00310","article-title":"Fast and Sensitive Detection of Oligosaccharides Using Desalting Paper Spray Mass Spectrometry (DPS-MS)","volume":"31","author":"Wang","year":"2020","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.ijms.2011.05.013","article-title":"Paper spray ionization devices for direct, biomedical analysis using mass spectrometry","volume":"312","author":"Yang","year":"2012","journal-title":"Int. J. Mass Spectrom."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4443","DOI":"10.1039\/c3an00934c","article-title":"Quantitative paper spray mass spectrometry analysis of drugs of abuse","volume":"138","author":"Su","year":"2013","journal-title":"Analyst"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"9158","DOI":"10.1021\/acs.analchem.1c01011","article-title":"Point-of-Care Test Paper for Exhaled Breath Aldehyde Analysis via Mass Spectrometry","volume":"93","author":"Li","year":"2021","journal-title":"Anal. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"116688","DOI":"10.1016\/j.ijms.2021.116688","article-title":"Desalting paper spay mass spectrometry (DPS-MS) for rapid detection of glycans and glycoconjugates","volume":"469","author":"Chiu","year":"2021","journal-title":"Int. J. Mass Spectrom."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1021\/jasms.0c00063","article-title":"Direct Analysis of Doping Agents in Raw Urine Using Hydrophobic Paper Spray Mass Spectrometry","volume":"31","author":"Rossini","year":"2020","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"6207","DOI":"10.1021\/acs.analchem.9b05078","article-title":"Schirmer Paper Noninvasive Microsampling for Direct Mass Spectrometry Analysis of Human Tears","volume":"92","author":"Yao","year":"2020","journal-title":"Anal. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"7988","DOI":"10.1021\/acs.analchem.7b01296","article-title":"Sub-ppt Mass Spectrometric Detection of Therapeutic Drugs in Complex Biological Matrixes Using Polystyrene-Microsphere-Coated Paper Spray","volume":"89","author":"Wang","year":"2017","journal-title":"Anal. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Chamberlain, C., Hatch, M., and Garrett, T. (2021). Extracellular Vesicle Analysis by Paper Spray Ionization Mass Spectrometry. Metabolites, 11.","DOI":"10.3390\/metabo11050308"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"16167","DOI":"10.1073\/pnas.2001395117","article-title":"Oral squamous cell carcinoma diagnosed from saliva metabolic profiling","volume":"117","author":"Song","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"166210","DOI":"10.1016\/j.bbadis.2021.166210","article-title":"A pilot study for colorectal carcinoma screening by instant metabolomic profiles using conductive polymer spray ionization mass spectrometry","volume":"1867","author":"Li","year":"2021","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. Basis Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1021\/jasms.0c00111","article-title":"Paper Spray Ionization Mass Spectrometry as a Potential Tool for Early Diagnosis of Cervical Cancer","volume":"31","author":"Mendes","year":"2020","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7774","DOI":"10.1021\/acs.analchem.1c00943","article-title":"Rapid Diagnosis of Prostate Cancer Disease Progression Using Paper Spray Ionization Mass Spectrometry","volume":"93","author":"Mahmud","year":"2021","journal-title":"Anal. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1021\/acs.analchem.9b03966","article-title":"Predicting Breast Cancer by Paper Spray Ion Mobility Spectrometry Mass Spectrometry and Machine Learning","volume":"92","author":"Huang","year":"2019","journal-title":"Anal. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.trac.2019.04.022","article-title":"Ion mobility spectrometry and the omics: Distinguishing isomers, molecular classes and contaminant ions in complex samples","volume":"116","author":"Zheng","year":"2019","journal-title":"TrAC Trends Anal. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6399","DOI":"10.1021\/acs.analchem.7b00075","article-title":"Ion Mobility, Hydrogen\/Deuterium Exchange, and Isotope Scrambling: Tools to Aid Compound Identification in \u2018Omics Mixtures","volume":"89","author":"Maleki","year":"2017","journal-title":"Anal. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4737","DOI":"10.1021\/acs.analchem.7b00683","article-title":"Gas-Phase Hydrogen\/Deuterium Exchange for Distinguishing Isomeric Carbohydrate Ions","volume":"89","author":"Uppal","year":"2017","journal-title":"Anal. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6259","DOI":"10.1021\/acs.analchem.9b00979","article-title":"Synthetic Small Molecule Characterization and Isomer Discrimination Using Gas-Phase Hydrogen\u2013Deuterium Exchange IMS-MS","volume":"91","author":"Kelly","year":"2019","journal-title":"Anal. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1021\/acs.jpcb.9b09919","article-title":"Effect of Transition-Metal Ions on the Conformation of Encephalin Investigated by Hydrogen\/Deuterium Exchange and Theoretical Calculations","volume":"124","author":"Wu","year":"2020","journal-title":"J. Phys. Chem. B"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.trac.2018.06.008","article-title":"Conformational analysis of complex protein states by hydrogen\/deuterium exchange mass spectrometry (HDX-MS): Challenges and emerging solutions","volume":"106","author":"Trabjerg","year":"2018","journal-title":"TrAC Trends Anal. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1007\/s13361-019-02163-0","article-title":"Rapid Solution-Phase Hydrogen\/Deuterium Exchange for Metabolite Compound Identification","volume":"30","author":"Majuta","year":"2019","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1021\/jasms.9b00069","article-title":"Teflon Spray Ionization Mass Spectrometry","volume":"31","author":"Narayanan","year":"2020","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"100048","DOI":"10.1016\/j.talo.2021.100048","article-title":"Polymer Substrate with Surface Solvent Reservoir for Polymer-Spray Mass Spectrometric Analysis of Hydrophilic Drugs","volume":"4","author":"Dulay","year":"2021","journal-title":"Talanta Open"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1002\/rcm.7952","article-title":"Polymer-spray mass spectrometric detection and quantitation of hydrophilic compounds and some narcotics","volume":"31","author":"Dulay","year":"2017","journal-title":"Rapid Commun. Mass Spectrom."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e4628","DOI":"10.1002\/jms.4628","article-title":"Coulometry--assisted quantitation in spray ionization mass spectrometry","volume":"56","author":"Song","year":"2021","journal-title":"J. Mass Spectrom."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"12878","DOI":"10.1021\/acs.analchem.8b03460","article-title":"Conductive Polymer Spray Ionization Mass Spectrometry for Biofluid Analysis","volume":"90","author":"Song","year":"2018","journal-title":"Anal. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"10411","DOI":"10.1021\/acs.analchem.1c02026","article-title":"Hydrogen\u2013Deuterium Exchange Desorption Electrospray Ionization Mass Spectrometry Visualizes an Acidic Tumor Microenvironment","volume":"93","author":"Song","year":"2021","journal-title":"Anal. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1021\/jasms.0c00260","article-title":"Tutorial: Chemistry of Hydrogen\/Deuterium Exchange Mass Spectrometry","volume":"32","author":"Hamuro","year":"2021","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s13361-018-2080-1","article-title":"Characterization of Electrospray Ionization (ESI) Parameters on In-ESI Hydrogen\/Deuterium Exchange of Carbohydrate-Metal Ion Adducts","volume":"30","author":"Liyanage","year":"2019","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1002\/mas.21565","article-title":"Hydrogen\/deuterium exchange in mass spectrometry","volume":"37","author":"Kostyukevich","year":"2018","journal-title":"Mass. Spec. Rev."}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/11\/11\/728\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:22:09Z","timestamp":1760167329000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/11\/11\/728"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,23]]},"references-count":32,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["metabo11110728"],"URL":"https:\/\/doi.org\/10.3390\/metabo11110728","relation":{"has-preprint":[{"id-type":"doi","id":"10.20944\/preprints202110.0035.v1","asserted-by":"object"}]},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,23]]}}}