Determination of docetaxel and metabolites in plasma by UPLC-MS/MS: method development and clinical application

A highly sensitive ultra-performance liquid chromatography tandem mass spectrometry method for the determination of Docetaxel and metabolites (M1+M3) in human plasma samples was developed and validated. The method employs a liquid-liquid extraction and a reversed phase separation Acquity® C18 column BEH C18 (150 x 2.1 mm, 1.7 µm). Mobile phase was a mixture of formic acid 0.1% (eluent A) and acetonitrile plus 0.1% formic acid (eluent B) in isocratic mode. Total analytical run time was 7 min. The interval of method linearity interval was 50 to 3000 ng mL-1 for docetaxel and 5.0 to 300 ng mL-1, for M1+M3 metabolites. Intra-assay and inter-assay precision was coefficient of variation 2.5-15.7% and 5.9-12.6%, respectively and accuracy was 89.0-114.0%. The method was successfully applied in the measurement of docetaxel plasma levels and area under the curve calculation in 31 cancer patients, demonstrating adequate analytical performance for the clinical application in the therapeutic drug monitoring and pharmacokinetics studies.