title: A liquid chromatography-electrospray ionization tandem mass spectrometric assay for quantitation of the histone deacetylase inhibitor, vorinostat (suberoylanilide hydroxamicacid, SAHA), and its metabolites in human serum.
abstract: Vorinostat (suberoylanilide hydroxamic acid, SAHA) is undergoing evaluation as an antineoplastic agent. We developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for quantitating vorinostat and its major metabolites, vorinostat glucuronide and 4-anilino-4-oxobutanoic acid, in human serum. The assay uses: deuterated internal standards; acetonitrile protein precipitation; a BDS Hypersil C18 (3 microm, 100 mm x 3 mm) column; a gradient mobile phase of 0.5% acetic acid in acetonitrile and water; and electrospray positive-mode ionization with selected reaction monitoring (SRM) detection. The lower limit of quantitation was 3.0 ng/ml for each analyte. The assay is being employed in at least 12 clinical studies of vorinostat-containing regimens.
authors.affiliation: Molecular Therapeutics/Drug Discovery Program, University of Pittsburgh Cancer Institute, PA 15213, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Parise
authors.forename: Julianne L
authors.initials: JL
authors.lastname: Holleran
authors.forename: Jan H
authors.initials: JH
authors.lastname: Beumer
authors.forename: Suresh
authors.initials: S
authors.lastname: Ramalingam
authors.forename: Merrill J
authors.initials: MJ
authors.lastname: Egorin
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods*; D004791:Enzyme Inhibitors / Q000097:blood*; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000097:blood*; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D000077337:Vorinostat
chemical_list: D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D000077337:Vorinostat