{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T07:04:41Z","timestamp":1792739081369,"version":"4.5.0"},"reference-count":48,"publisher":"American Chemical Society (ACS)","issue":"9","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["1R35GM146671-01"],"award-info":[{"award-number":["1R35GM146671-01"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Enantiomers play important roles in biology and the pharmaceutical industry but remain notoriously difficult to separate and characterize. Gold-standard chromatography and nuclear magnetic resonance-based methods are slow, laborious, and expensive, motivating the development of rapid methodologies for enantiomer characterization. While ion mobility spectrometry-mass spectrometry (IMS-MS) has emerged as a rapid technique for chiral analysis, current approaches often rely on derivatization, complicated chiral complexes, or large host molecules that can produce complex spectra. Herein, we investigate small carbohydrates as chiral adducts for the ion mobility separation of amino acid and drug enantiomers. Six commercially available nonreducing or reduced carbohydrates were evaluated as chiral adduct molecules using cyclic IMS-MS. All carbohydrate adducts readily formed simple 1:1 complexes in the MS dimension that produced two discrete IMS peaks for each enantiomeric pair and remained sufficiently stable for extended path length separations. The carbohydrate panel enabled chiral separation of all 15 amino acid and drug enantiomer pairs at pathlengths as low as 1 m. Relative arrival time measurements further enabled unbiased comparison of separation performance across analyte-adduct pairs. The developed carbohydrate-based method was used to quantify enantiomeric excess down to a 99:1 molar ratio with estimated limits of detection down to 5 nM. These results demonstrate that small carbohydrates are effective chiral adducts for IMS-MS-based enantiomer separations and that simple analyte-adduct complexes can provide rapid and broadly applicable enantiomer differentiation without derivatization or the use of multimolecule complexes.<\/jats:p>","DOI":"10.1021\/jasms.6c00250","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T12:01:42Z","timestamp":1786536102000},"page":"2228-2237","source":"Crossref","is-referenced-by-count":1,"title":["Chiral Carbohydrate\nAdducts are Effective for Enantiomeric\nIon Mobility Separations"],"prefix":"10.1021","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-3509-1845","authenticated-orcid":true,"given":"Noah D.","family":"Roberts","sequence":"first","affiliation":[{"name":"University of Utah , , 315 South 1400 East, Room 2020 , , ,","place":["Salt Lake City, Utah, United States, 84112"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9007-4422","authenticated-orcid":true,"given":"Gabe","family":"Nagy","sequence":"additional","affiliation":[{"name":"University of Utah , , 315 South 1400 East, Room 2020 , , ,","place":["Salt Lake City, Utah, United States, 84112"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"2026090311510532800_cit1","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.trac.2016.01.016","article-title":"State-of-the-art enantioseparations\nof natural and unnatural amino acids by high-performance liquid chromatography","volume":"81","author":"Ilisz","year":"2016","journal-title":"TrAC, Trends Anal. Chem."},{"issue":"1","key":"2026090311510532800_cit2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/toxsci\/kfr088","article-title":"Thalidomide: The Tragedy of Birth\nDefects and the Effective\nTreatment of Disease","volume":"122","author":"Kim","year":"2011","journal-title":"Toxicol. Sci."},{"issue":"8","key":"2026090311510532800_cit3","doi-asserted-by":"publisher","first-page":"6003","DOI":"10.1021\/acs.analchem.5c06382","article-title":"Chiral Derivatization\nEnables High-Resolution Ion Mobility Spectrometry of 30 Amino Acid\nEnantiomers","volume":"98","author":"Yan","year":"2026","journal-title":"Anal. Chem."},{"issue":"47","key":"2026090311510532800_cit4","doi-asserted-by":"publisher","first-page":"14114","DOI":"10.1039\/D2SC03604E","article-title":"Chiral derivatization-enabled\ndiscrimination and on-tissue detection of proteinogenic amino acids\nby ion mobility mass spectrometry","volume":"13","author":"Xie","year":"2022","journal-title":"Chem. Sci."},{"issue":"1","key":"2026090311510532800_cit5","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.cclet.2017.06.009","article-title":"Chiral\nderivatization coupled with liquid chromatography\/mass spectrometry\nfor determining ketone metabolites of hydroxybutyrate enantiomers","volume":"29","author":"Cheng","year":"2018","journal-title":"Chin. Chem. Lett."},{"issue":"8","key":"2026090311510532800_cit6","doi-asserted-by":"publisher","DOI":"10.1002\/chir.23705","article-title":"Enantiomeric\nAnalysis of Chiral Drugs Using Mass Spectrometric\nMethods: A Comprehensive Review","volume":"36","author":"Vallamkonda","year":"2024","journal-title":"Chirality"},{"key":"2026090311510532800_cit7","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.chroma.2012.10.033","article-title":"Recent developments\non polysaccharide-based chiral stationary phases for liquid-phase\nseparation of enantiomers","volume":"1269","author":"Chankvetadze","year":"2012","journal-title":"J. Chromatogr. A"},{"issue":"2","key":"2026090311510532800_cit8","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1021\/ac202892w","article-title":"Chiral Separations:\nA Review of Current Topics and\nTrends","volume":"84","author":"Ward","year":"2012","journal-title":"Anal. Chem."},{"key":"2026090311510532800_cit9","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/978-1-4939-6403-1_15","article-title":"Enantiomer Separations by Capillary\nElectrophoresis","volume-title":"Capillary Electrophoresis:\nMethods and Protocols","author":"Scriba","year":"2016"},{"issue":"2","key":"2026090311510532800_cit10","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1002\/chir.23386","article-title":"Molecular enantiodiscrimination\nby NMR spectroscopy in chiral oriented\nsystems: Concept, tools, and applications","volume":"34","author":"Aroulanda","year":"2022","journal-title":"Chirality"},{"issue":"12","key":"2026090311510532800_cit11","doi-asserted-by":"publisher","DOI":"10.1002\/ajoc.202200544","article-title":"Chiral\nAnalysis of Pharmaceuticals Using NMR Spectroscopy: A Review","volume":"11","author":"Vashistha","year":"2022","journal-title":"Asian J. Org. Chem."},{"issue":"8","key":"2026090311510532800_cit12","doi-asserted-by":"publisher","first-page":"1692","DOI":"10.1021\/ac001150v","article-title":"Mass Spectrometric\nQuantitation of\nChiral Drugs by the Kinetic Method","volume":"73","author":"Tao","year":"2001","journal-title":"Anal. Chem."},{"issue":"2","key":"2026090311510532800_cit13","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1255\/ejms.749","article-title":"Chiral and Isomeric\nAnalysis by Electrospray Ionization\nand Sonic Spray Ionization Using the Fixed-Ligand Kinetic Method","volume":"11","author":"Wu","year":"2005","journal-title":"Eur. J. Mass Spectrom."},{"issue":"4","key":"2026090311510532800_cit14","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1007\/s13361-014-1072-z","article-title":"Complete Hexose\nIsomer Identification with Mass Spectrometry","volume":"26","author":"Nagy","year":"2015","journal-title":"J. Am. Soc. Mass Spectrom."},{"issue":"4","key":"2026090311510532800_cit15","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1002\/mas.21902","article-title":"Recent advances in\nhigh-resolution traveling wave-based ion mobility\nseparations coupled to mass spectrometry","volume":"44","author":"Naylor","year":"2025","journal-title":"Mass\nSpectrom. Rev."},{"issue":"1","key":"2026090311510532800_cit16","doi-asserted-by":"publisher","first-page":"952","DOI":"10.1021\/acs.analchem.6b04171","article-title":"Investigation of the Complete Suite\nof the Leucine and Isoleucine Isomers: Toward Prediction of Ion Mobility\nSeparation Capabilities","volume":"89","author":"Dodds","year":"2017","journal-title":"Anal. Chem."},{"issue":"31","key":"2026090311510532800_cit17","doi-asserted-by":"publisher","first-page":"12892","DOI":"10.1021\/acs.analchem.4c02710","article-title":"Direct\nEnantiomer Differentiation of Drugs and Drug-Like Compounds via Noncovalent\nCopper\u2013Amino Acid Complexation and Ion Mobility-Mass Spectrometry","volume":"96","author":"Blakley","year":"2024","journal-title":"Anal. Chem."},{"issue":"6","key":"2026090311510532800_cit18","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1021\/jasms.2c00059","article-title":"Enantiomer\nDifferentiation of Amino\nAcid Stereoisomers by Structural Mass Spectrometry Using Noncovalent\nTrinuclear Copper Complexes","volume":"33","author":"Zlibut","year":"2022","journal-title":"J. Am. Soc. Mass\nSpectrom."},{"key":"2026090311510532800_cit19","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.aca.2017.05.026","article-title":"Chiral differentiation of amino acids through binuclear\ncopper bound tetramers by ion mobility mass spectrometry","volume":"981","author":"Yu","year":"2017","journal-title":"Anal. Chim. Acta"},{"issue":"4","key":"2026090311510532800_cit20","doi-asserted-by":"publisher","first-page":"2335","DOI":"10.1021\/acs.analchem.5b04280","article-title":"Multidimensional\nAnalysis of 16 Glucose Isomers by Ion Mobility Spectrometry","volume":"88","author":"Gaye","year":"2016","journal-title":"Anal. Chem."},{"issue":"7","key":"2026090311510532800_cit21","doi-asserted-by":"publisher","first-page":"2850","DOI":"10.1021\/ac0618627","article-title":"Enantiomer Separation\nof Amino Acids by Complexation\nwith Chiral Reference Compounds and High-Field Asymmetric Waveform\nIon Mobility Spectrometry: Preliminary Results and Possible Limitations","volume":"79","author":"Mie","year":"2007","journal-title":"Anal. Chem."},{"issue":"8","key":"2026090311510532800_cit22","doi-asserted-by":"publisher","first-page":"3234","DOI":"10.1039\/C4SC00443D","article-title":"Enantiomeric differentiation of aromatic\namino acids using traveling wave ion mobility-mass spectrometry","volume":"5","author":"Domalain","year":"2014","journal-title":"Chem. Sci."},{"issue":"24","key":"2026090311510532800_cit23","doi-asserted-by":"publisher","first-page":"3148","DOI":"10.1002\/elps.201800294","article-title":"Distinguishing enantiomeric\namino acids with chiral cyclodextrin adducts and structures for lossless\nion manipulations","volume":"39","author":"Nagy","year":"2018","journal-title":"Electrophoresis"},{"issue":"4","key":"2026090311510532800_cit24","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1021\/acsmeasuresciau.2c00016","article-title":"Evaluating the Utility of Temporal Compression in High-Resolution\nTraveling Wave-Based Cyclic Ion Mobility Separations","volume":"2","author":"Williamson","year":"2022","journal-title":"ACS Meas. Sci. Au"},{"key":"2026090311510532800_cit25","doi-asserted-by":"publisher","DOI":"10.1016\/j.talanta.2022.123363","article-title":"The chirality determination\nof amino acids by forming complexes with cyclodextrins and metal ions\nusing ion mobility spectrometry, and a DFT calculation","volume":"243","author":"Yang","year":"2022","journal-title":"Talanta"},{"issue":"12","key":"2026090311510532800_cit26","doi-asserted-by":"publisher","first-page":"2474","DOI":"10.1002\/jssc.202100025","article-title":"Direct\ndistinction\nof ibuprofen and flurbiprofen enantiomers by ion mobility mass spectrometry\nof their ternary complexes with metal cations and cyclodextrins in\nthe gas phase","volume":"44","author":"Gu","year":"2021","journal-title":"J. Sep. Sci."},{"issue":"45","key":"2026090311510532800_cit27","doi-asserted-by":"publisher","first-page":"15096","DOI":"10.1021\/acs.analchem.1c03378","article-title":"Identification of\nBi-2-naphthol and Its Phosphate Derivatives Complexed with Cyclodextrin\nand Metal Ions Using Trapped Ion Mobility Spectrometry","volume":"93","author":"Wang","year":"2021","journal-title":"Anal. Chem."},{"issue":"13","key":"2026090311510532800_cit28","doi-asserted-by":"publisher","first-page":"8564","DOI":"10.1021\/acs.analchem.9b01838","article-title":"A Cyclic Ion Mobility-Mass Spectrometry\nSystem","volume":"91","author":"Giles","year":"2019","journal-title":"Anal. Chem."},{"issue":"8","key":"2026090311510532800_cit29","doi-asserted-by":"publisher","first-page":"4628","DOI":"10.1021\/acs.analchem.7b00185","article-title":"Serpentine Ultralong\nPath with Extended Routing (SUPER) High Resolution Traveling Wave\nIon Mobility-MS using Structures for Lossless Ion Manipulations","volume":"89","author":"Deng","year":"2017","journal-title":"Anal. Chem."},{"issue":"7","key":"2026090311510532800_cit30","doi-asserted-by":"publisher","first-page":"3160","DOI":"10.1021\/acs.analchem.3c05594","article-title":"Cyclable Variable Path Length Multilevel\nStructures for Lossless Ion Manipulations (SLIM) Platform for Enhanced\nIon Mobility Separations","volume":"96","author":"Huntley","year":"2024","journal-title":"Anal. Chem."},{"issue":"11","key":"2026090311510532800_cit31","doi-asserted-by":"publisher","first-page":"2185","DOI":"10.1007\/s13361-019-02288-2","article-title":"Ion Mobility Spectrometry: Fundamental Concepts, Instrumentation,\nApplications, and the Road Ahead","volume":"30","author":"Dodds","year":"2019","journal-title":"J. Am. Soc.\nMass Spectrom."},{"issue":"2","key":"2026090311510532800_cit32","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1021\/acs.analchem.0c03461","article-title":"Effective Chiral Discrimination\nof Amino Acids through Oligosaccharide\nIncorporation by Trapped Ion Mobility Spectrometry","volume":"93","author":"Xie","year":"2021","journal-title":"Anal. Chem."},{"issue":"11","key":"2026090311510532800_cit33","doi-asserted-by":"publisher","first-page":"2204","DOI":"10.1007\/s13361-019-02333-0","article-title":"Separation and Identification\nof Glycan Anomers Using Ultrahigh-Resolution Ion-Mobility Spectrometry\nand Cryogenic Ion Spectroscopy","volume":"30","author":"Warnke","year":"2019","journal-title":"J. Am. Soc.\nMass Spectrom."},{"issue":"6","key":"2026090311510532800_cit34","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.1007\/s13361-019-02168-9","article-title":"Cyclic Ion\nMobility Mass Spectrometry Distinguishes Anomers and Open-Ring Forms\nof Pentasaccharides","volume":"30","author":"Ujma","year":"2019","journal-title":"J. Am. Soc. Mass Spectrom."},{"issue":"83","key":"2026090311510532800_cit35","doi-asserted-by":"publisher","first-page":"11701","DOI":"10.1039\/C8CC06966B","article-title":"Unraveling the isomeric heterogeneity\nof glycans: ion mobility separations in structures for lossless ion\nmanipulations","volume":"54","author":"Nagy","year":"2018","journal-title":"Chem. Commun."},{"issue":"10","key":"2026090311510532800_cit36","doi-asserted-by":"publisher","first-page":"2573","DOI":"10.1021\/jasms.1c00207","article-title":"Investigating\nthe Structure of \u03b1\/\u03b2\nCarbohydrate Linkage Isomers as a Function of Group I Metal Adduction\nand Degree of Polymerization as Revealed by Cyclic Ion Mobility Separations","volume":"32","author":"Williamson","year":"2021","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"2026090311510532800_cit37","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.ijms.2012.01.016","article-title":"Investigating the relationship between\nthe gas-phase\nconformations and dissociation energetics of peptide\u2013saccharide\ncomplexes","volume":"316\u2013318","author":"Comeau","year":"2012","journal-title":"Int. J. Mass Spectrom."},{"issue":"11","key":"2026090311510532800_cit38","doi-asserted-by":"publisher","first-page":"2480","DOI":"10.1021\/jasms.5c00227","article-title":"Space Charge\nInduced Dissociation\nDue to Extended Ion Accumulation Preceding Cyclic Ion Mobility Separation","volume":"36","author":"Mane","year":"2025","journal-title":"J. Am. Soc. Mass Spectrom."},{"issue":"14","key":"2026090311510532800_cit39","doi-asserted-by":"publisher","first-page":"5775","DOI":"10.1021\/ac201509p","article-title":"Effective\nTemperature of Ions in\nTraveling Wave Ion Mobility Spectrometry","volume":"83","author":"Morsa","year":"2011","journal-title":"Anal.\nChem."},{"issue":"10","key":"2026090311510532800_cit40","doi-asserted-by":"publisher","DOI":"10.1002\/rcm.8764","article-title":"Exploration of disaccharide\nas reference towards chiral recognition by the kinetic method","volume":"34","author":"Huang","year":"2020","journal-title":"Rapid Commun. Mass Spectrom."},{"issue":"37","key":"2026090311510532800_cit41","doi-asserted-by":"publisher","first-page":"13992","DOI":"10.1021\/acs.analchem.3c02619","article-title":"Coupling Isotopic Shifts\nwith Collision Cross-Section Measurements\nfor Carbohydrate Characterization in High-Resolution Ion Mobility\nSeparations","volume":"95","author":"Williamson","year":"2023","journal-title":"Anal. Chem."},{"issue":"8","key":"2026090311510532800_cit42","doi-asserted-by":"publisher","first-page":"1737","DOI":"10.1021\/jasms.5c00112","article-title":"Developing Reduced\nMass-Only Ion Mobility Separations to Unravel\nMass Distribution-Based Isotopic Shifts","volume":"36","author":"Roberts","year":"2025","journal-title":"J.\nAm. Soc. Mass Spectrom."},{"issue":"23","key":"2026090311510532800_cit43","doi-asserted-by":"publisher","first-page":"11877","DOI":"10.1021\/acs.analchem.6b03660","article-title":"Squeezing of Ion\nPopulations and Peaks in Traveling\nWave Ion Mobility Separations and Structures for Lossless Ion Manipulations\nUsing Compression Ratio Ion Mobility Programming","volume":"88","author":"Garimella","year":"2016","journal-title":"Anal. Chem."},{"issue":"1","key":"2026090311510532800_cit44","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1021\/acs.analchem.5c05855","article-title":"Spatial Ion Compression\nwithout Loss\nof Resolution on a Cyclic Ion Mobility Spectrometry\u2013Mass Spectrometry\nPlatform","volume":"98","author":"Robinson","year":"2026","journal-title":"Anal. Chem."},{"issue":"14","key":"2026090311510532800_cit45","doi-asserted-by":"publisher","first-page":"9482","DOI":"10.1021\/acs.analchem.9b05718","article-title":"Resolution of Isomeric\nMixtures in Ion Mobility Using a Combined Demultiplexing and Peak\nDeconvolution Technique","volume":"92","author":"May","year":"2020","journal-title":"Anal. Chem."},{"issue":"22","key":"2026090311510532800_cit46","doi-asserted-by":"publisher","first-page":"16449","DOI":"10.1021\/acs.analchem.6c01528","article-title":"High-Resolution Ion Mobility-Based Isotopic Shifts of Dimethylated\nPeptide Isomers","volume":"98","author":"Roberts","year":"2026","journal-title":"Anal. Chem."},{"issue":"9","key":"2026090311510532800_cit47","doi-asserted-by":"publisher","first-page":"1692","DOI":"10.1021\/jasms.2c00136","article-title":"Quantitation of\nEnantiomeric Excess in an Achiral Environment Using Trapped Ion Mobility\nMass Spectrometry","volume":"33","author":"Czekner","year":"2022","journal-title":"J. Am. Soc. Mass Spectrom."},{"issue":"45","key":"2026090311510532800_cit48","doi-asserted-by":"publisher","first-page":"33429","DOI":"10.1039\/D4RA05694A","article-title":"The significance of chirality in contemporary drug\ndiscovery-a mini review","volume":"14","author":"Senkuttuvan","year":"2024","journal-title":"RSC Adv."}],"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.6c00250","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jamsef\/article-pdf\/37\/9\/2228\/66507911\/jasms.6c00250.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jamsef\/article-pdf\/37\/9\/2228\/66507911\/jasms.6c00250.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T16:23:52Z","timestamp":1788452632000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jamsef\/article\/37\/9\/2228\/5253251\/Chiral-Carbohydrate-Adducts-are-Effective-for"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,12]]},"references-count":48,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,8,12]]},"published-print":{"date-parts":[[2026,9,2]]}},"URL":"https:\/\/doi.org\/10.1021\/jasms.6c00250","relation":{},"ISSN":["1044-0305","1879-1123"],"issn-type":[{"value":"1044-0305","type":"print"},{"value":"1879-1123","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,12]]}}}