Determination of SNX-2112, a selective Hsp90 inhibitor, in plasma samples by high-performance liquid chromatography and its application to pharmacokinetics in rats.

A sensitive and specific reversed-phase high-performance liquid chromatography method with ultraviolet detection has been developed and validated for the identification and quantification of SNX-2112 in rat plasma. Following sample preparation using liquid-liquid extraction, the analytes were separated by the mobile phase acetonitrile-water (40:60, v/v) with an Agilent RP-HPLC column (ZORBAX SB-C18, 5 microm, 4.6 mm x 250 mm) at a flow rate of 1 ml/min, column temperature of 30 degrees C and detection wavelength of 251 nm. The retention time of SNX-2112 was 11.2 min. A good linear relationship was obtained in the concentration range studied (0.07-21 microg/ml, R(2)>0.9982), and the LLOD and LLOQ for SNX-2112 were 0.02 and 0.07 microg/ml, respectively. The mean absolute recovery of SNX-2112 in plasma ranged from 88.58 to 99.61% at the studied concentrations. The intra- and inter-batch relative standard deviations were 1.7-3.5 and 1.9-4.4%, respectively. This method was successfully applied to pharmacokinetic studies in rats after intravenous administration of SNX-2112.