A sensitive and specific liquid chromatography-tandem mass spectrometric method for determination of belinostat in plasma from liver cancer patients
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AbstractA novel, sensitive and reliable liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the determination of belinostat (PXD101) in human plasma. Oxamflatin was used as the internal standard. Liquid-liquid extraction of the plasma sample was performed using tert-butyl methyl ether as the organic solvent. Chromatographic separation was achieved on a BDS Hypersil C18 column (2.1 mm x 100 mm, 5 mu m) using gradient elution mode using 0.05% formic acid in water and 0.05% formic acid in acetonitrile as solvents A and B, respectively, 60/40. The run time was 6 min. The mass spectrometer was operated under a positive electrospray ionization condition and a multiple reaction monitoring mode. An excellent linear calibration was achieved in the range of 0.5-1000 ng/mL. An average recovery of belinostat for four quality controls was 72.6% and the recovery of the internal standard at 1000 ng/mL was 67.8%. The intra-day and inter-day precisions for belinostat were <= 8.0 and <= 10.3%, respectively, and their accuracy ranged from 100.2 to 106.7%. No significant matrix effect was identified. In analysis of patient samples, belinostat glucuronide was identified and baseline separated from belinostat. This well-validated assay has been applied for quantification of belinostat in plasma samples within 24 h after the start of infusion for Asian hepatocellular carcinoma patients in a dose escalation study. (C) 2010 Elsevier By. All rights reserved.
All Author(s) ListWang LZ, Chan D, Yeo W, Wan SC, Chan S, Chan A, Lee SC, Lee HS, Goh BC
Journal nameJournal of Chromatography B
Detailed description[Epub ahead of print].
Volume Number878
Issue Number26
Pages2409 - 2414
LanguagesEnglish-United Kingdom
KeywordsBelinostat; Belinostat glucuronide; Human plasma; LC-MS/MS
Web of Science Subject CategoriesBiochemical Research Methods; BIOCHEMICAL RESEARCH METHODS; Biochemistry & Molecular Biology; Chemistry; Chemistry, Analytical; CHEMISTRY, ANALYTICAL

Last updated on 2020-28-11 at 00:19