{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T12:29:16Z","timestamp":1766492956891,"version":"build-2065373602"},"reference-count":36,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,4,28]],"date-time":"2021-04-28T00:00:00Z","timestamp":1619568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Ceramides have been implicated in a number of disease processes. However, current means of evaluation with flow infusion analysis (FIA) have been limited primarily due to poor sensitivity within our high-resolution mass spectrometry lipidomics analytical platform. To circumvent this deficiency, we investigated the potential of chloride adducts as an alternative method to improve sensitivity with electrospray ionization. Chloride adducts of ceramides and ceramide subfamilies provided 2- to 50-fold increases in sensitivity both with analytical standards and biological samples. Chloride adducts of a number of other lipids with reactive hydroxy groups were also enhanced. For example, monogalactosyl diacylglycerols (MGDGs), extracted from frontal lobe cortical gray and subcortical white matter of cognitively intact subjects, were not detected as ammonium adducts but were readily detected as chloride adducts. Hydroxy lipids demonstrate a high level of specificity in that phosphoglycerols and phosphoinositols do not form chloride adducts. In the case of choline glycerophospholipids, the fatty acid substituents of these lipids could be monitored by MS2 of the chloride adducts. Monitoring the chloride adducts of a number of key lipids offers enhanced sensitivity and specificity with FIA. In the case of glycerophosphocholines, the chloride adducts also allow determination of fatty acid substituents. The chloride adducts of lipids possessing electrophilic hydrogens of hydroxyl groups provide significant increases in sensitivity. In the case of glycerophosphocholines, chloride attachment to the quaternary ammonium group generates a dominant anion, which provides the identities of the fatty acid substituents under MS2 conditions.<\/jats:p>","DOI":"10.3390\/life11050403","type":"journal-article","created":{"date-parts":[[2021,4,28]],"date-time":"2021-04-28T10:41:58Z","timestamp":1619606518000},"page":"403","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Human Brain Lipidomics: Utilities of Chloride Adducts in Flow Injection Analysis"],"prefix":"10.3390","volume":"11","author":[{"given":"Paul L.","family":"Wood","sequence":"first","affiliation":[{"name":"Metabolomics Unit, College of Veterinary Medicine, Lincoln Memorial University, 6965 Cumberland Gap Pkwy, Harrogate, TN 37752, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen A.","family":"Hauther","sequence":"additional","affiliation":[{"name":"Anatomy Department, DeBusk College of Osteopathic Medicine, Lincoln Memorial University, 6965 Cumberland Gap Pkwy, Harrogate, TN 37752, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jon H.","family":"Scarborough","sequence":"additional","affiliation":[{"name":"Medicine Department, DeBusk College of Osteopathic Medicine, Lincoln Memorial University, 6965 Cumberland Gap Pkwy, Harrogate, TN 37752, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dustin J.","family":"Craney","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Indiana University School of Medicine, 340 West 10th St, Indianapolis, IN 46202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatrix","family":"Dudzik","sequence":"additional","affiliation":[{"name":"Anatomy Department, DeBusk College of Osteopathic Medicine, Lincoln Memorial University, 6965 Cumberland Gap Pkwy, Harrogate, TN 37752, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John E.","family":"Cebak","sequence":"additional","affiliation":[{"name":"Neurology, Mayo Clinic, 5711 E. Mayo Blvd., Phoenix, AZ 85054, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Randall L.","family":"Woltjer","sequence":"additional","affiliation":[{"name":"Department of Pathology, Oregon Health Science University, 3181 SW Sam Jackson PK. Rd., Portland, OR 97239, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,28]]},"reference":[{"key":"ref_1","first-page":"20","article-title":"Trends Ceramides as novel disease biomarkers","volume":"25","author":"Kurz","year":"2019","journal-title":"Mol. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2070","DOI":"10.1073\/pnas.0305799101","article-title":"Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer\u2019s disease","volume":"101","author":"Cutler","year":"2004","journal-title":"Proc. Natl. Acad. Sci. 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