title: High-throughput plasma docetaxel quantification by liquid chromatography-tandem mass spectrometry.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Experimental and Clinical Pharmacology, Department of Molecular Biology and Translational Research, National Cancer Institute and Center for Molecular Biomedicine, Aviano (PN), Italy. giuseppe.corona@cro.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Corona
authors.forename: Caterina
authors.initials: C
authors.lastname: Elia
authors.forename: Bruno
authors.initials: B
authors.lastname: Casetta
authors.forename: Sergio
authors.initials: S
authors.lastname: Frustaci
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Toffoli
mesh_terms: D001774:Blood Chemical Analysis / Q000191:economics / Q000379:methods*; D002853:Chromatography, Liquid / Q000191:economics / Q000379:methods*; D017321:Clinical Trials, Phase I as Topic; D000077143:Docetaxel; D006801:Humans; D057230:Limit of Detection; D016014:Linear Models; D009862:Online Systems; D053719:Tandem Mass Spectrometry / Q000191:economics / Q000379:methods*; D043823:Taxoids / Q000097:blood* / Q000493:pharmacokinetics; D013997:Time Factors
chemical_list: D043823:Taxoids; D000077143:Docetaxel