A sensitive and specific liquid chromatography-tandem mass spectrometric method for determination of belinostat in plasma from liver cancer patients.
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.
Wang
Ling-Zhi
LZ
Cancer Science Institute of Singapore, National University of Singapore, Singapore. csiwl@nus.edu.sg
Chan
Daniel
D
Yeo
Winnie
W
Wan
Seow-Ching
SC
Chan
Stephen
S
Chan
Anthony
A
Lee
Soo-Chin
SC
Lee
How-Sung
HS
Goh
Boon-Cher
BC
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*
D000970:Antineoplastic Agents; D006877:Hydroxamic Acids; D013449:Sulfonamides; C100692:oxamflatin; C487081:belinostat