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J Chromatogr B Analyt Technol Biomed Life Sci ; 879(30): 3452-8, 2011 Nov 15.
Article in English | MEDLINE | ID: mdl-21983196

ABSTRACT

A rapid and sensitive liquid chromatography/tandem mass spectrometry (LC-MS/MS) method has been developed and fully validated to determine HS270, a new histone deacetylase (HDAC) inhibitor, in rat plasma using SAHA as the internal standard (IS). After a single step liquid-liquid extraction with acetoacetate, analytes were subjected to LC-MS/MS analysis using positive electro-spray ionization (ESI(+)) under selected reaction monitoring mode (SRM). The chromatographic separation was achieved on a Hypurity C(18) column (50 mm × 2.1 mm, i.d., 5 µm). The MS/MS detection was conducted by monitoring the fragmentation of m/z 392.3→100.1 for HS270, m/z 265.1→232.1 for IS. The method had a chromatographic running time of 2.5 min and linear calibration curves over the concentrations of 0.5-1000 ng/mL. The recovery of the method was 70.8-82.5% and the lower limit of quantification (LLOQ) was 0.5 ng/mL. The intra- and inter-batch precisions were less than 15% for all quality control samples at concentrations of 1.0, 100.0, and 750.0 ng/mL. The validated LC-MS/MS method has successfully applied to a HS270 pharmacokinetic study after oral doses of 25, 50, 100, 200 mg/kg, and i.v. dose of 5 mg/kg to rats.


Subject(s)
Chromatography, Liquid/methods , Histone Deacetylase Inhibitors/blood , Tandem Mass Spectrometry/methods , Administration, Oral , Animals , Histone Deacetylase Inhibitors/administration & dosage , Histone Deacetylase Inhibitors/chemistry , Histone Deacetylase Inhibitors/pharmacokinetics , Hydroxamic Acids/analysis , Linear Models , Rats , Reproducibility of Results , Sensitivity and Specificity , Spectrometry, Mass, Electrospray Ionization , Vorinostat
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