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Drift DTIMS provides additional precursor ion selectivity and collisional cross-section information but the separation resolution between analytes remains cell- and component-dependent. With DMS, the addition of 2-propanol modifier can improve the selectivity but on cost of analyte MS response. In the present work, we investigate the liquid chromatography\u2013mass spectrometry (LC\u2013MS) analysis of a\u00a0mix of 50 analytes, representative for urine and plasma metabolites, using scanning DMS with the\u00a0single modifiers cyclohexane (Ch), toluene (Tol), acetonitrile (ACN), ethanol (EtOH), and\u00a02-propanol (IPA), and a\u00a0binary modifier mixture (cyclohexane\/2-propanol) with emphasis on selectivity and signal sensitivity. 1.5% IPA in the N<jats:sub>2<\/jats:sub> stream was found to suppress the signal of 50% of the analytes which could be partially recovered with the use of IPA to 0.05% as a Ch\/IPA mixture. The potential to use the\u00a0separation voltage\/compensation voltage\/modifier (SV\/CoV\/Mod) feature as an additional analyte identifier for qualitative analysis is also presented and applied to a data-independent LCxDMS-SWATH-MS workflow for the analysis of endogenous metabolites and drugs of abuse in human urine samples from traffic control.<\/jats:p>\n                <jats:p><jats:bold>Graphical Abstract<\/jats:bold><\/jats:p>","DOI":"10.1007\/s00216-023-04602-0","type":"journal-article","created":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T06:56:38Z","timestamp":1677135398000},"page":"1905-1915","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Liquid chromatography and differential mobility spectrometry\u2014data-independent mass spectrometry for comprehensive multidimensional separations in metabolomics"],"prefix":"10.1007","volume":"415","author":[{"given":"Lysi","family":"Ekmekciu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9087-606X","authenticated-orcid":false,"given":"G\u00e9rard","family":"Hopfgartner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,2,23]]},"reference":[{"issue":"5","key":"4602_CR1","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1016\/j.cbpa.2013.06.015","volume":"17","author":"R Ramautar","year":"2013","unstructured":"Ramautar R, Berger R, van der Greef J, Hankemeier T. 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