title: A liquid chromatography/tandem mass spectrometry assay to quantitate MS-275 in human plasma.
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).
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Rudek
authors.forename: Aleksandr
authors.initials: A
authors.lastname: Mnasakanyan
authors.forename: Carol
authors.initials: C
authors.lastname: Hartke
authors.forename: Roberto
authors.initials: R
authors.lastname: Pili
authors.forename: Sharyn D
authors.initials: SD
authors.lastname: Baker
mesh_terms: D000085:Acetates / Q000737:chemistry; D000097:Acetonitriles / Q000737:chemistry; D000970:Antineoplastic Agents / Q000097:blood* / Q000494:pharmacology; D001549:Benzamides / Q000097:blood* / Q000494:pharmacology; D002073:Butanes / Q000737:chemistry; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000592:standards; D004355:Drug Stability; D004791:Enzyme Inhibitors / Q000097:blood; D005561:Formates / Q000737:chemistry; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006863:Hydrogen-Ion Concentration; D016018:Least-Squares Analysis; D015394:Molecular Structure; D009369:Neoplasms / Q000097:blood; D011725:Pyridines / Q000097:blood* / Q000494:pharmacology; D012044:Regression Analysis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012997:Solvents / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods* / Q000592:standards; D053719:Tandem Mass Spectrometry / Q000379:methods* / Q000592:standards
chemical_list: D000085:Acetates; D000097:Acetonitriles; D000970:Antineoplastic Agents; D001549:Benzamides; D002073:Butanes; D004791:Enzyme Inhibitors; D005561:Formates; D056572:Histone Deacetylase Inhibitors; D011725:Pyridines; D012997:Solvents; C030544:formic acid; C118739:entinostat; C018824:ammonium acetate; C032159:acetonitrile; C006854:butyl chloride