A sensitive docetaxel assay in plasma by solid-phase extraction and high performance liquid chromatography-UV detection: Validation and suitability in phase I clinical trial pharmacokinetics

We have developed a specific and sensitive method aiming at docetaxel (Taxo tere(R)) determination in plasma of treated patients. This involved solid-p hase extraction of 1 ml of plasma onto carboxylic acid (CBA) grafted silica cartridges followed by reversed-phase liquid chromatography with UV detect ion. The best selectivity was obtained through the use of C18 Uptisphere(R) as stationary phase. The low limit of quantitation obtained (LOQ: 5 ng/ml) allowed measurements of docetaxel up to 24 hours after one-hour infusions with low dosages of drug (60 mg/m(2)). The method was applied successfully to monitor docetaxel plasma levels within two protocols associating fixed d osages of either methotrexate or gemcitabine with escalating doses of Taxot ere(R).