title: A sensitive and specific liquid chromatography-tandem mass spectrometric method for determination of belinostat in plasma from liver cancer patients.
abstract: A 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 x1 00 mm, 5 microm) 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 <or=8.0 and <or=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 24h after the start of infusion for Asian hepatocellular carcinoma patients in a dose escalation study.
authors: Cancer Science Institute of Singapore, National University of Singapore, Singapore. csiwl@nus.edu.sg
authors: Ling-Zhi
authors: LZ
authors: Wang
authors: Daniel
authors: D
authors: Chan
authors: Winnie
authors: W
authors: Yeo
authors: Seow-Ching
authors: SC
authors: Wan
authors: Stephen
authors: S
authors: Chan
authors: Anthony
authors: A
authors: Chan
authors: Soo-Chin
authors: SC
authors: Lee
authors: How-Sung
authors: HS
authors: Lee
authors: Boon-Cher
authors: BC
authors: Goh
mesh_terms: D000970:Antineoplastic Agents / Q000097:blood* / Q000737:chemistry; D005591:Chemical Fractionation; D002853:Chromatography, Liquid / Q000379:methods*; D002986:Clinical Trials as Topic; D006801:Humans; D006877:Hydroxamic Acids / Q000032:analysis / Q000097:blood* / Q000737:chemistry; D016018:Least-Squares Analysis; D008113:Liver Neoplasms / Q000097:blood*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013449:Sulfonamides; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D006877:Hydroxamic Acids; D013449:Sulfonamides; C100692:oxamflatin; C487081:belinostat