A liquid chromatography/tandem mass spectrometry assay to quantitate MS-275 in human plasma

J Pharm Biomed Anal. 2007 Jan 17;43(2):784-7. doi: 10.1016/j.jpba.2006.08.006. Epub 2006 Sep 12.

Abstract

A rapid, sensitive and selective method was developed and validated using LC/MS/MS for determination of MS-275 in human plasma. Sample preparation involved a single step liquid-liquid extraction by the addition of 0.2 ml of plasma with 5 ml acetonitrile/n-butyl-chloride. Separation of the compounds of interest, including the internal standard paclitaxel, was achieved on a Waters X-Terra C(18) (50 mm x 2.1mm i.d., 3.5 microm) analytical column using a mobile phase consisting of acetonitrile/ammonium acetate (pH 2.9; 2mM)(60:40, v/v) containing 0.1% formic acid and isocratic flow at 0.15 ml/min for 3 min. The analytes were monitored by tandem-mass spectrometry with electrospray positive ionization. Linear calibration curves were generated over the range of 0.5-100 ng/ml with values for the coefficient of determination of >0.99. The values for both within day and between day precision and accuracy were well within the generally accepted criteria for analytical methods (<15%). This method was subsequently used to measure concentrations of MS-275 in cancer patients receiving an oral weekly dose of 4 mg/m(2).

Publication types

  • Validation Study

MeSH terms

  • Acetates / chemistry
  • Acetonitriles / chemistry
  • Antineoplastic Agents / blood*
  • Antineoplastic Agents / pharmacology
  • Benzamides / blood*
  • Benzamides / pharmacology
  • Butanes / chemistry
  • Calibration
  • Chromatography, High Pressure Liquid / methods*
  • Chromatography, High Pressure Liquid / standards
  • Drug Stability
  • Enzyme Inhibitors / blood
  • Formates / chemistry
  • Histone Deacetylase Inhibitors
  • Humans
  • Hydrogen-Ion Concentration
  • Least-Squares Analysis
  • Molecular Structure
  • Neoplasms / blood
  • Pyridines / blood*
  • Pyridines / pharmacology
  • Regression Analysis
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Solvents / chemistry
  • Spectrometry, Mass, Electrospray Ionization / methods*
  • Spectrometry, Mass, Electrospray Ionization / standards
  • Tandem Mass Spectrometry / methods*
  • Tandem Mass Spectrometry / standards

Substances

  • Acetates
  • Acetonitriles
  • Antineoplastic Agents
  • Benzamides
  • Butanes
  • Enzyme Inhibitors
  • Formates
  • Histone Deacetylase Inhibitors
  • Pyridines
  • Solvents
  • formic acid
  • entinostat
  • ammonium acetate
  • acetonitrile
  • butyl chloride