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Despite its versatility, the presence of background ions in MS analysis hinders the sensitive detection of low\u2010abundance analytes. Therefore, studies aimed at lowering background ion levels have become increasingly important. Here, we utilized the commercially available Active Background Ion Reduction Device (ABIRD) to suppress background ions and assess its effect on the liquid chromatography\u2013electrospray ionization (LC\u2013ESI)\u2013MS analyses of <jats:italic>N<\/jats:italic>\u2010glycans on the Q Exactive HF mass spectrometer. We also investigated the effect of different solvent vapors in the ESI source on <jats:italic>N<\/jats:italic>\u2010glycan analysis by MS. ABIRD generally had no effect on high\u2010mannose and neutral structures but reduced the intensity of some structures that contained sialic acid, fucose, or both when methanol vapor filled the ESI source. Based on our findings on the highest number of identified <jats:italic>N<\/jats:italic>\u2010glycans from human serum, methanol vapor in the ion source compartment may enhance <jats:italic>N<\/jats:italic>\u2010glycan LC\u2013ESI\u2013MS analyses by improving the desolvation of droplets formed during the ESI process due to its high volatility. This protocol may be further validated and extended to advanced bottom\u2010up proteomic\/glycoproteomic studies for the analysis of peptide\/glycopeptide ions by MS.<\/jats:p>","DOI":"10.1002\/elps.202300301","type":"journal-article","created":{"date-parts":[[2024,4,4]],"date-time":"2024-04-04T09:25:51Z","timestamp":1712222751000},"page":"1469-1478","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Suppressing the background of LC\u2013ESI\u2013MS analysis of permethylated glycans using the active background ion reduction device"],"prefix":"10.1002","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9168-5396","authenticated-orcid":false,"given":"Mojibola","family":"Fowowe","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry Texas Tech University  Lubbock Texas 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