title: Quantification of low molecular weight selenium metabolites in human plasma after treatment with selenite in pharmacological doses by LC-ICP-MS.
abstract: The paper presents an analytical method for quantification of low molecular weight (LMW) selenium compounds in human plasma based on liquid chromatography inductively coupled plasma mass spectrometry (LC-ICP-MS) and post column isotope dilution-based quantification. Prior to analysis, samples were ultrafiltrated using a cut-off value of 3000 Da. The method was validated in aqueous solution as well as plasma using standards of selenomethionine (SeMet), Se-methylselenocysteine (MeSeCys), selenite, and the selenosugar Se-methylseleno-N-acetylgalactosamine (SeGal) for linearity, precision, recoveries, and limits of detection and quantitation with satisfactory results. The method was applied for analysis of a set of plasma samples from cancer patients receiving selenite treatment in a clinical trial. Three LMW selenium compounds were observed. The main compounds, SeGal and selenite were tentatively identified by retention time matching with standards in different chromatographic systems, while the third minor compound was not identified. The identity of the selenosugar was verified by ESI-MS-MS product ion scanning, while selenite was identified indirectly as the glutathione (GSH) reaction product, GS-Se-SG.
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark.
authors.forename: Konstantina
authors.initials: K
authors.lastname: Flouda
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark.
authors.forename: Julie Maria
authors.initials: JM
authors.lastname: Dersch
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Gabel-Jensen
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark.
authors.forename: Stefan
authors.initials: S
authors.lastname: Stürup
authors.affiliation: Division of Pathology F46, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86, Stockholm, Sweden.
authors.forename: Sougat
authors.initials: S
authors.lastname: Misra
authors.affiliation: Division of Pathology F46, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86, Stockholm, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Björnstedt
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark. bente.gammelgaard@sund.ku.dk.
authors.forename: Bente
authors.initials: B
authors.lastname: Gammelgaard
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D002853:Chromatography, Liquid; D006801:Humans; D057230:Limit of Detection; D013058:Mass Spectrometry; D008970:Molecular Weight; D009369:Neoplasms / Q000188:drug therapy; D012015:Reference Standards; D020887:Selenious Acid / Q000008:administration & dosage* / Q000627:therapeutic use; D012643:Selenium / Q000097:blood*
chemical_list: D000970:Antineoplastic Agents; D020887:Selenious Acid; D012643:Selenium
keywords: ESI-MS; LC-ICP-MS; Plasma; Selenium; Speciation