A sensitive and specific assay for paclitaxel in plasma has been developed to overcome limitations in previously published assays, using liquid chromatography with tandem mass spectrometric detection. Plasma samples (100 µL) were subjected to liquid-liquid extraction with 1-chlorobutane/acetonitrile (4:1, v/v), with [2H5]paclitaxel employed as the internal standard. Chromatography was carried out with a Waters SymmetryShield C8 column (50 × 2.1 mm, 3.5 µm). The total run time, including equilibration, was 8 min, using a gradient of acetonitrile and 10 mM ammonium formate, pH 4.0. The assay is accurate and precise over the range of 2–2500 ng/mL and has been successfully applied to study the clinical pharmacokinetics of two formulations of paclitaxel, Genaxol and Genetaxyl, given orally and intravenously. Copyright © 2006 John Wiley & Sons, Ltd.