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

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 mu m, 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 vormostat-containing regimens. (c) 2006 Elsevier B.V. All rights reserved.