High-throughput plasma docetaxel quantification by liquid chromatography-tandem mass spectrometry

Background: The most valuable treatment option for breast, prostate and lung carcinomas is at present represented by a low dose of docetaxel, administered on a weekly basis. A better understanding of docetaxel pharmacokinetic and pharmacodynamic profiles could lead to an improvement in this dose regimen efficacy. Methods: In this study a high-throughput method is described for the rapid quantification of docetaxel for large clinical pharmacology investigations. This analytical approach is based on an automatic on-line purification and enrichment technique followed by a measurement in tandem mass spectrometry through Multiple Reaction Monitoring. Results: The assay was validated over a 0.15-1500 ng/mL range. Intra-day precision ranged from 1.9% to 6.4%, while the inter-day was between 7.6% and 11.2%. The mean deviation from the nominal value ranged from -0.5% to 5.6% for the intra-day, and from -0.4% to 3.1% for the inter-day assay. Clinical applicability was demonstrated by measuring plasma pharmacokinetics in patients receiving weekly 25-35 mg/m(2) of docetaxel. Conclusion: The proposed LC-MS/MS assay was found to have a better performance than previously reported methods in terms of sensitivity and sample preparation. It does not require any laborious pre-analytical manipulation and can be easily employed in large clinical pharmacology studies. (C) 2010 Elsevier B.V. All rights reserved.