文摘
A quantitative method for the simultaneous determinationof docetaxel (Taxotere), paclitaxel (Taxol), 6G SRC="/images/gifchars/alpha.gif" BORDER=0>-hydroxypaclitaxel, and p-3'-hydroxypaclitaxel in human plasmaand oral fluid is developed and validated. Oral fluid (thisterm is now preferred to saliva) was sampled with aSalivette collection device. The procedure used a simpleliquid/liquid extraction with methyl tert-butyl ether followed by LC-ESI-MS/MS. Gradient elution was appliedand provided increased robustness to ion suppression bythe 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 positiveion mode were monitored through multiple reactionmonitoring. Calibration was performed by internal standardization with cephalomannine, and regression curveswere constructed ranging between 2 and 1000 ng/mL inplasma and 0.125 and 62.5 ng/mL in oral fluid, using aweighing factor of 1/x2. The regression curves werequadratic for paclitaxel and docetaxel and linear for thepaclitaxel metabolites. Accuracy varied from 91.3 to103.6%, and imprecision did not exceed 12.7% for allanalytes in plasma and oral fluid. In conclusion, a sensitive and robust method was obtained, which fulfilled allvalidation criteria.