title: Development and validation of a liquid chromatography-tandem mass spectrometry assay for the quantification of docetaxel and paclitaxel in human plasma and oral fluid.
abstract: A quantitative method for the simultaneous determination of docetaxel (Taxotere), paclitaxel (Taxol), 6alpha-hydroxypaclitaxel, and p-3'-hydroxypaclitaxel in human plasma and oral fluid is developed and validated. Oral fluid (this term is now preferred to saliva) was sampled with a Salivette collection device. The procedure used a simple liquid/liquid extraction with methyl tert-butyl ether followed by LC-ESI-MS/MS. Gradient elution was applied and provided increased robustness to ion suppression by the drug formulation vehicle (polysorbate 80 and Cremophor EL). Adduct ion formation with sodium and potassium was noticed and controlled by mobile-phase optimization. The protonated analytes generated in the positive ion mode were monitored through multiple reaction monitoring. Calibration was performed by internal standardization with cephalomannine, and regression curves were constructed ranging between 2 and 1000 ng/mL in plasma and 0.125 and 62.5 ng/mL in oral fluid, using a weighing factor of 1/x2. The regression curves were quadratic for paclitaxel and docetaxel and linear for the paclitaxel metabolites. Accuracy varied from 91.3 to 103.6%, and imprecision did not exceed 12.7% for all analytes in plasma and oral fluid. In conclusion, a sensitive and robust method was obtained, which fulfilled all validation criteria.
authors: Laboratory of Toxicology, Ghent University, Harelbekestraat 72, B-9000 Ghent, Belgium.
authors: Kjell A
authors: KA
authors: Mortier
authors: Vincent
authors: V
authors: Renard
authors: Alain G
authors: AG
authors: Verstraete
authors: Annie
authors: A
authors: Van Gussem
authors: Simon
authors: S
authors: Van Belle
authors: Willy E
authors: WE
authors: Lambert
mesh_terms: D000970:Antineoplastic Agents / Q000032:analysis / Q000097:blood; D002853:Chromatography, Liquid / Q000379:methods*; D000077143:Docetaxel; D004355:Drug Stability; D006801:Humans; D015394:Molecular Structure; D017239:Paclitaxel / Q000032:analysis* / Q000097:blood*; D015203:Reproducibility of Results; D012463:Saliva / Q000737:chemistry*; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D043823:Taxoids / Q000032:analysis* / Q000097:blood*
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel