Determination of docetaxel in rat plasma and its application in the comparative pharmacokinetics of Taxotere and SID530, a novel docetaxel formulation with hydroxypropyl-beta-cyclodextrin

Abstract

In this study, a sensitive, simple and reliable method for the quantification of docetaxel in rat plasma was developed and validated using liquid chromatographytandem mass spectrometry (LC-MS/MS). The plasma samples were prepared by protein precipitation, and paclitaxel was used as an internal standard (IS). Chromatographic separation was achieved using a Gemini C18 column (2.0x150mm, 5 mu m) with a mobile phase consisting of 0.1% formic acidacetonitrile (30:70, v/v). The precursorproduct ion pairs used for multiple reaction monitoring were m/z 808.5527.5 (docetaxel) and m/z 854.2286.5 (IS, paclitaxel). A calibration curve for docetaxel was constructed over the range 11000ng/mL. The developed method was specific, precise and accurate, and no matrix effect was observed. The validated method was applied in a comparative pharmacokinetic study in which two docetaxel formulations, SID530, a new parenteral formulation of docetaxel with hydroxypropyl--cyclodextrin (HP--CD), and Taxotere, were administered to rats at a dose of 5mg/kg. For SID530 and Taxotere, the mean C0 values were 1494 and 1818ng/mL, respectively, and the AUClast values were 837 and 755hng/mL, respectively. These two formulations did not show any statistical differences with regard to the pharmacokinetic parameters, thus establishing that the SID530 and Taxotere products are pharmacokinetically comparable in male rats. Copyright (c) 2012 John Wiley & Sons, Ltd.