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However, some important compounds, such as the antiepileptic drug valproate (valproic acid; VPA), cannot be directly detected with positive electrospray ionization (ESI<jats:sup>+<\/jats:sup>) due to poor ionization. Here we demonstrate an omics\u2010based retrospective analysis for the identification of indirect screening targets for VPA in whole blood with LC\u2013ESI<jats:sup>+<\/jats:sup>\u2013HRMS. Analysis was performed utilizing data acquired across four years from LC\u2013ESI<jats:sup>+<\/jats:sup>\u2013HRMS, with VPA results from a quantitative LC\u2013MS\/MS method. The combined data with VPA results were split into an exploration set (<jats:italic>n<\/jats:italic>\u00a0=\u00a068; 28% positive) and a test set (<jats:italic>n<\/jats:italic>\u00a0=\u00a037; 32% positive). Eight indirect targets for VPA were identified in the exploration set. The evaluation of these targets was confirmed with retrospective target analysis of the test set. Using a combination of two out of the eight indirect targets, we attained a sensitivity of 92% (<jats:italic>n<\/jats:italic>\u00a0=\u00a012; VPA concentration range: 4.4\u201329.7\u00a0mg\/kg) and 100% specificity (<jats:italic>n<\/jats:italic>\u00a0=\u00a025) for VPA with LC\u2013ESI<jats:sup>+<\/jats:sup>\u2013HRMS. VPA screening targets were identified with retrospective data analysis and could be appended to the existing screening procedure. A sensitive and specific screening with LC\u2013ESI<jats:sup>+<\/jats:sup>\u2013HRMS was achieved with targets corresponding to the sodium adducts of C<jats:sub>7<\/jats:sub>H<jats:sub>14<\/jats:sub>O<jats:sub>3<\/jats:sub> and C<jats:sub>8<\/jats:sub>H<jats:sub>14<\/jats:sub>O<jats:sub>3<\/jats:sub>. Three chromatographic resolved isomer peaks were observed for the latter, and the consistently most intense peak was tentatively identified as 3\u2010hydroxy\u20104\u2010en\u2010VPA.<\/jats:p>","DOI":"10.1002\/dta.2543","type":"journal-article","created":{"date-parts":[[2018,11,13]],"date-time":"2018-11-13T23:44:59Z","timestamp":1542152699000},"page":"730-738","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Retrospective analysis for valproate screening targets with liquid chromatography\u2013high resolution mass spectrometry with positive electrospray ionization: An omics\u2010based approach"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8187-6474","authenticated-orcid":false,"given":"Christian Brinch","family":"Mollerup","sequence":"first","affiliation":[{"name":"Section of Forensic Chemistry, Department of Forensic Medicine, Faculty of Health and Medical Sciences 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