{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T12:49:06Z","timestamp":1785847746603,"version":"3.56.0"},"reference-count":35,"publisher":"American Chemical Society (ACS)","issue":"30","license":[{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000854","name":"Human Frontier Science Program","doi-asserted-by":"publisher","award":["RGP0002\/2022"],"award-info":[{"award-number":["RGP0002\/2022"]}],"id":[{"id":"10.13039\/501100000854","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013699","name":"Bundesministerium Bildung","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100013699","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"Grantov? Agentura Cesk? Republiky","doi-asserted-by":"publisher","award":["24-10736S"],"award-info":[{"award-number":["24-10736S"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"Ministerstvo ?kolstv?, Ml?de?e a Telov?chovy","doi-asserted-by":"publisher","award":["CZ.02.01.01\/00\/22_008\/0004607"],"award-info":[{"award-number":["CZ.02.01.01\/00\/22_008\/0004607"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]}],"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>Gangliosides are structurally complex glycosphingolipids that regulate cellular signaling via interactions with extracellular binding partners and by influencing protein function within the membrane. Their comprehensive analysis remains analytically challenging, in part due to low endogenous abundance, extensive structural diversity, and the frequent occurrence of isomeric species arising from both glycan and ceramide moieties. Here, we present a hydrophilic interaction liquid chromatography (HILIC) nanoelectrospray ionization tandem mass spectrometry (nanoESI-MS\/MS) method specifically designed to achieve isomer-resolved analysis and molecular species-level quantification of gangliosides. To improve characterization of low-abundance fatty acyl fragments, the workflow was extended by combining nanoESI with online fraction collection and subsequent direct infusion. The method demonstrated stable chromatographic performance, high sensitivity, and reproducible quantitative results across ten mouse tissues. Application of the workflow enabled quantification of 80 ganglioside molecular species belonging to 18 subclasses and revealed pronounced tissue-specific differences in subclass distribution and ceramide composition. Overall, this study establishes a robust and sensitive platform for comprehensive ganglioside analysis, providing new opportunities to investigate ganglioside diversity, regulation, and function in complex biological systems.<\/jats:p>","DOI":"10.1021\/acs.analchem.6c00380","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T18:33:57Z","timestamp":1783362837000},"page":"22068-22079","source":"Crossref","is-referenced-by-count":0,"title":["Comprehensive\nIsomer-Resolved Ganglioside Profiling\nby HILIC-nanoESI-MS\/MS"],"prefix":"10.1021","volume":"98","author":[{"given":"Nina","family":"Troppmair","sequence":"first","affiliation":[{"name":"University of Vienna , , ,","place":["Vienna, Austria, 1090"]},{"name":"University of Vienna , , ,","place":["Vienna, Austria, 1090"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Santol","sequence":"additional","affiliation":[{"name":"Medical University of Vienna , , ,","place":["Vienna, Austria, 1090"]},{"name":"Clinic Favoriten and Sigmund Freud Private University , , ,","place":["Vienna, Austria, 1100"]},{"name":"Mayo Clinic , , , ,","place":["Rochester, Minnesota, United States, 55905"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Baumert","sequence":"additional","affiliation":[{"name":"Advion Ltd, Harlow Enterprise Hub , ,","place":["Harlow, United Kingdom, CM20 2NQ"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1379-1406","authenticated-orcid":true,"given":"Luka\u0301s\u030c","family":"Opa\u0301lka","sequence":"additional","affiliation":[{"name":"Charles University , , ,","place":["Hradec Kra\u0301love\u0301, Czech Republic, 500 03"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Assinger","sequence":"additional","affiliation":[{"name":"Medical University of Vienna , , ,","place":["Vienna, Austria, 1090"]},{"name":"Ludwig Boltzmann Institute of Cardiovascular Research , ,","place":["Vienna, Austria, 1090"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3771-2410","authenticated-orcid":true,"given":"Cristina","family":"Coman","sequence":"additional","affiliation":[{"name":"University of Vienna , , ,","place":["Vienna, Austria, 1090"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0232-3375","authenticated-orcid":true,"given":"Robert","family":"Ahrends","sequence":"additional","affiliation":[{"name":"University of Vienna , , ,","place":["Vienna, Austria, 1090"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,6]]},"reference":[{"issue":"5","key":"2026080408080210300_cit1","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1194\/jlr.E400004-JLR200","article-title":"A comprehensive classification\nsystem for lipids","volume":"46","author":"Fahy","year":"2005","journal-title":"J. Lipid Res."},{"issue":"22","key":"2026080408080210300_cit2","doi-asserted-by":"publisher","first-page":"12425","DOI":"10.1021\/acs.analchem.7b03523","article-title":"Hydrophilic\nInteraction Liquid Chromatography\u2013Mass\nSpectrometry Characterization of Gangliosides in Biological Samples","volume":"89","author":"Ha\u0301jek","year":"2017","journal-title":"Anal. Chem."},{"key":"2026080408080210300_cit3","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.aca.2020.12.022","article-title":"High-defined quantitative\nsnapshots of the ganglioside lipidome using high resolution ion mobility\nSLIM assisted shotgun lipidomics","volume":"1146","author":"Moser","year":"2021","journal-title":"Anal. Chim.\nActa"},{"key":"2026080408080210300_cit4","doi-asserted-by":"publisher","DOI":"10.5402\/2012\/506160","article-title":"Ganglioside\nBiochemistry","volume":"2012","author":"Kolter","year":"2012","journal-title":"ISRN Biochem."},{"key":"2026080408080210300_cit5","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/j.aca.2020.05.051","article-title":"Recent advances in the mass spectrometric analysis of glycosphingolipidome\n\u2013 A review","volume":"1132","author":"Barrientos","year":"2020","journal-title":"Anal. Chim. Acta"},{"key":"2026080408080210300_cit6","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1002\/mas.20294","article-title":"Lipidomics era: Accomplishments\nand challenges","volume":"29","author":"Khalil","year":"2010","journal-title":"Mass Spectrom. Rev."},{"key":"2026080408080210300_cit7","doi-asserted-by":"publisher","DOI":"10.1002\/rcm.9041","article-title":"An integrated Qual\/Quan strategy for ganglioside lipidomics\nusing high-resolution mass spectrometry and Skyline software","volume":"35","author":"Ranasinghe","year":"2021","journal-title":"Rapid Commun. Mass Spectrom."},{"issue":"1","key":"2026080408080210300_cit8","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/0005-2760(80)90227-1","article-title":"A procedure\nfor the quantitative isolation of brain\ngangliosides","volume":"617","author":"Svennerholm","year":"1980","journal-title":"Biochim. Biophys. Acta, Lipids\nLipid Metab."},{"issue":"1","key":"2026080408080210300_cit9","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/s0021-9258(18)64849-5","article-title":"A simple method\nfor the isolation\nand purification of total lipides from animal tissues","volume":"226","author":"Folch","year":"1957","journal-title":"J. Biol. Chem."},{"issue":"8","key":"2026080408080210300_cit10","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1139\/y59-099","article-title":"A rapid method of total lipid extraction\nand purification","volume":"37","author":"Bligh","year":"1959","journal-title":"Can. J. Biochem. Physiol."},{"issue":"11","key":"2026080408080210300_cit11","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.105323","article-title":"Ganglioside lipidomics\nof CNS myelination using\ndirect infusion shotgun mass spectrometry","volume":"25","author":"Arends","year":"2022","journal-title":"iScience"},{"issue":"1","key":"2026080408080210300_cit12","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-53032-8","article-title":"Deciphering mouse\nbrain spatial diversity via glyco-lipidomic mapping","volume":"15","author":"Lee","year":"2024","journal-title":"Nat. Commun."},{"issue":"8","key":"2026080408080210300_cit13","doi-asserted-by":"publisher","first-page":"1797","DOI":"10.1194\/jlr.D050302","article-title":"A monophasic extraction\nstrategy\nfor the simultaneous lipidome analysis of polar and nonpolar retina\nlipids","volume":"55","author":"Lydic","year":"2014","journal-title":"J. Lipid Res."},{"key":"2026080408080210300_cit14","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2019.121956","article-title":"Rapid sample\npreparation for ganglioside analysis by liquid chromatography mass\nspectrometry","volume":"1137","author":"Khoury","year":"2020","journal-title":"J. Chromatogr. B"},{"issue":"8","key":"2026080408080210300_cit15","doi-asserted-by":"publisher","first-page":"1335","DOI":"10.1194\/jlr.D200005-JLR200","article-title":"Recovery of\ngangliosides from aqueous solutions on styrene-divinylbenzene copolymer\ncolumns1","volume":"43","author":"Popa","year":"2002","journal-title":"J. Lipid Res."},{"key":"2026080408080210300_cit16","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1385\/0-89603-355-4:183","article-title":"TLC\nin Structure and Recognition Studies of Glycosphingolipids","volume-title":"Glycoanalysis Protocols","author":"Mu\u0308thing","year":"1998"},{"key":"2026080408080210300_cit17","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1016\/j.bbrc.2008.12.086","article-title":"Obesity causes a shift in metabolic\nflow of gangliosides in adipose tissues","volume":"379","author":"Tanabe","year":"2009","journal-title":"Biochem.\nBiophys. Res. Commun."},{"issue":"11","key":"2026080408080210300_cit18","doi-asserted-by":"publisher","first-page":"2466","DOI":"10.1021\/jacsau.2c00230","article-title":"Decoding Distinct Ganglioside Patterns of Native and\nDifferentiated Mesenchymal Stem Cells by a Novel Glycolipidomics Profiling\nStrategy","volume":"2","author":"Hohenwallner","year":"2022","journal-title":"JACS Au"},{"key":"2026080408080210300_cit19","doi-asserted-by":"publisher","DOI":"10.1021\/ac402379y","article-title":"Structural Characterization\nof Gangliosides and Glycolipids\nvia Ultraviolet Photodissociation Mass Spectrometry","volume":"85","author":"O\u2019Brien","year":"2013","journal-title":"Anal. Chem."},{"key":"2026080408080210300_cit20","doi-asserted-by":"publisher","first-page":"2330","DOI":"10.1007\/s13361-017-1772-2","article-title":"Structural\nAnalysis of Unsaturated Glycosphingolipids\nUsing Shotgun Ozone-Induced Dissociation Mass Spectrometry","volume":"28","author":"Barrientos","year":"2017","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"2026080408080210300_cit21","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1111\/j.1749-6632.2012.06479.x","article-title":"Beyond glycoproteins as galectin\ncounterreceptors: tumor-effector T cell growth control via ganglioside\nGM1","volume":"1253","author":"Ledeen","year":"2012","journal-title":"Ann. N.Y. Acad. Sci."},{"key":"2026080408080210300_cit22","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1016\/j.expneurol.2012.03.023","article-title":"A common mechanism\nand a new categorization for anti-ganglioside antibody-mediated neuropathies","volume":"235","author":"Uncini","year":"2012","journal-title":"Exp. Neurol."},{"key":"2026080408080210300_cit23","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1023\/B:GLYC.0000044844.95878.cf","article-title":"Carbohydrate-to-carbohydrate\ninteraction, through glycosynapse, as a basis of cell recognition\nand membrane organization","volume":"21","author":"Hakomori","year":"2004","journal-title":"Glycoconjugate J."},{"key":"2026080408080210300_cit24","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1016\/j.chemphyslip.2011.09.005","article-title":"Gangliosides and the\nmultiscale modulation of membrane structure","volume":"164","author":"Cantu\u0300","year":"2011","journal-title":"Chem. Phys. Lipids"},{"issue":"9","key":"2026080408080210300_cit25","doi-asserted-by":"publisher","first-page":"1870","DOI":"10.1016\/j.bpj.2012.09.018","article-title":"Importance of the\nSphingoid Base Length for the Membrane Properties of Ceramides","volume":"103","author":"Maula","year":"2012","journal-title":"Biophys. J."},{"issue":"12","key":"2026080408080210300_cit26","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2022.184036","article-title":"Impact of sphingomyelin acyl chain\nheterogeneity upon properties of raft-like membranes","volume":"1864","author":"Hirano","year":"2022","journal-title":"Biochim. Biophys. Acta, Biomembr."},{"issue":"4","key":"2026080408080210300_cit27","doi-asserted-by":"publisher","first-page":"1435","DOI":"10.1074\/mcp.M115.053702","article-title":"Simultaneous Metabolite,\nProtein, Lipid Extraction\n(SIMPLEX): A Combinatorial Multimolecular Omics Approach for Systems\nBiology","volume":"15","author":"Coman","year":"2016","journal-title":"Mol. Cell. Proteomics"},{"issue":"4","key":"2026080408080210300_cit28","doi-asserted-by":"publisher","first-page":"1447","DOI":"10.1021\/acs.jproteome.9b00640","article-title":"Skyline for Small Molecules: A Unifying Software\nPackage for Quantitative Metabolomics","volume":"19","author":"Adams","year":"2020","journal-title":"J. Proteome\nRes."},{"key":"2026080408080210300_cit29","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0029851","article-title":"LipidXplorer: A Software for Consensual\nCross-Platform Lipidomics","volume":"7","author":"Herzog","year":"2012","journal-title":"PLoS One"},{"issue":"1","key":"2026080408080210300_cit30","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2011-12-1-r8","article-title":"A novel informatics concept for high-throughput\nshotgun lipidomics based on the molecular fragmentation query language","volume":"12","author":"Herzog","year":"2011","journal-title":"Genome Biol."},{"key":"2026080408080210300_cit31","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1007\/978-3-540-78246-9_38","article-title":"KNIME:\nThe Konstanz Information Miner","volume-title":"Data Analysis,\nMachine Learning and Applications. Studies in Classification, Data\nAnalysis, and Knowledge Organization","author":"Berthold","year":"2008"},{"issue":"1","key":"2026080408080210300_cit32","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-59755-6","article-title":"Extended coverage of human serum\nglycosphingolipidome by 4D-RP-LC TIMS-PASEF unravels association with\nParkinson\u2019s disease","volume":"16","author":"Vo","year":"2025","journal-title":"Nat. Commun."},{"issue":"6","key":"2026080408080210300_cit33","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1002\/mas.21492","article-title":"Selection of internal standards for\naccurate quantification of complex lipid species in biological extracts\nby electrospray ionization mass spectrometry-What, how and why?","volume":"36","author":"Wang","year":"2017","journal-title":"Mass Spectrom. Rev."},{"issue":"1","key":"2026080408080210300_cit34","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109797","article-title":"Multiomics\nof synaptic junctions reveals altered\nlipid metabolism and signaling following environmental enrichment","volume":"37","author":"Borgmeyer","year":"2021","journal-title":"Cell Rep."},{"issue":"11","key":"2026080408080210300_cit35","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109250","article-title":"A reference map of\nsphingolipids\nin murine tissues","volume":"35","author":"Muralidharan","year":"2021","journal-title":"Cell Rep."}],"container-title":["Analytical Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.analchem.6c00380","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/ancham\/article-pdf\/98\/30\/22068\/65801392\/acs.analchem.6c00380.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/ancham\/article-pdf\/98\/30\/22068\/65801392\/acs.analchem.6c00380.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T12:23:04Z","timestamp":1785846184000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/ancham\/article\/98\/30\/22068\/5201881\/Comprehensive-Isomer-Resolved-Ganglioside"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,6]]},"references-count":35,"journal-issue":{"issue":"30","published-online":{"date-parts":[[2026,7,6]]},"published-print":{"date-parts":[[2026,8,4]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.analchem.6c00380","relation":{},"ISSN":["0003-2700","1520-6882"],"issn-type":[{"value":"0003-2700","type":"print"},{"value":"1520-6882","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,6]]}}}