title: Development and validation of a liquid chromatography-tandem mass spectrometry for the determination of Kendine 91, a novel histone deacetylase inhibitor, in mice plasma and tissues: application to a pharmacokinetic study.
abstract: A liquid chromatography-tandem mass spectrometric method (LC-MS/MS) has been developed and validated to determine the concentration of Kendine 91 in mice plasma and tissues. Simvastatin was employed as the internal standard. Separation was performed on a C8 column, with a mobile phase consisting of methanol and aqueous 10 mM formic acid (73:27 v/v). Both analyte and internal standard were determined using electrospray ionization and the MS data acquisition was via multiple-reaction monitoring (MRM) in positive scanning mode. Quantification was performed using the transitions m/z 444-->169 and 441-->325 for Kendine 91 and simvastatin, respectively. The method was validated with respect to linearity, accuracy, precision, recovery and stability. This assay has been successfully applied to a pharmacokinetic study after intravenous injection of Kendine 91 in mice in a dose of 10mg/kg.
authors.affiliation: Organic Chemistry Department, Faculty of Chemistry, University of the Basque Country, Edificio Joxe Mari Korta, Av Tolosa 72, San Sebastián, Spain.
authors.forename: Dorleta
authors.initials: D
authors.lastname: Otaegui
authors.forename: Alicia
authors.initials: A
authors.lastname: Rodríguez-Gascón
authors.forename: Aizpea
authors.initials: A
authors.lastname: Zubia
authors.forename: Fernando P
authors.initials: FP
authors.lastname: Cossío
authors.forename: José Luis
authors.initials: JL
authors.lastname: Pedraz
mesh_terms: D000818:Animals; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D004791:Enzyme Inhibitors / Q000032:analysis* / Q000097:blood / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D056572:Histone Deacetylase Inhibitors; D051379:Mice; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors