Determination of a benzamide histone deacetylase inhibitor, MS-275, in human plasma by liquid chromatography with mass-spectrometric detection

Abstract

An analytical method was developed and validated for the quantitative determination of the histone deacetylase inhibitor MS-275 in human plasma. Calibration curves were linear in the concentration range of 1–250 ng/mL. Sample pretreatment involved a liquid–liquid extraction of 0.1 mL aliquots of plasma with methyl tert-butyl ether. MS-275 and the internal standard, benzanilide, were separated on a Zorbax SB-Phenyl column (4.6 mm × 75 mm I.D., 3.5 μm), using a mobile phase composed of methanol and 10 mM ammonium formate (pH 2.9). The column eluent was monitored by mass spectrometry with electrospray ionization. Accuracy and precision of three concentrations of quality control samples ranged from 96.56 to 107.02% and 0.97 to 4.29%, respectively. This method represents an improvement over the previously published analytical assay for this agent, increasing the accuracy and precision (through addition of a suitable internal standard) and expanding the analytical range. The developed method was applied to study the pharmacokinetics of MS-275 in 724 clinical samples.