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

被引:52
作者
Parise, Robert A.
Holleran, Julianne L.
Beumer, Jan H.
Ramalingam, Suresh
Egorin, Merrill J. [1 ]
机构
[1] Univ Pittsburgh, Inst Canc, Mol Therapeut Drug Discovery Program, Pittsburgh, PA 15213 USA
[2] Univ Pittsburgh, Sch Med, Div Hematol Oncol, Dept Med, Pittsburgh, PA 15213 USA
[3] Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15213 USA
来源
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES | 2006年 / 840卷 / 02期
关键词
vorinostat; suberoylanilide hydroxamic acid; SAHA; histone deacetylase inhibitor; LC-MS/MS;
D O I
10.1016/j.jchromb.2006.04.044
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:108 / 115
页数:8
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