The Quantification of Paclitaxel and Its Two Major Metabolites in Biological Samples by HPLC-MS/MS and Its Application in a Pharmacokinetic and Tumor Distribution Study in Xenograft Nude Mouse.

ABSTRACT

A rapid and sensitive high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed for the quantification of Paclitaxel (PTX), 6α-hydroxypaclitaxel (6α-OHP), and p-3'-hydroxypaclitaxel (3'-OHP) in mouse plasma and tumor tissue. The analytes were separated using a C18 column (50 × 2.1 mm, 1.8 µm), and a triple-quadrupole mass spectrometry device equipped with an electrospray ionization (ESI) source was applied for their detection. PTX, 6α-OHP, and 3'-OHP were extracted from the biological samples with the solid-phase extraction cartridge. The method was fully validated according to the FDA's guidance. The method was linear over the concentration ranges of 0.5~1000.0 ng/mL for PTX and 0.25~500.0 ng/mL for 6α-OHP and 3'-OHP. The precision, accuracy, extraction recovery, and matrix effects were within acceptable limits. The present method was successfully applied to the study of the pharmacokinetics and distribution of PTX, 6α-OHP, and 3'-OHP in the tumors of post xenograft nude mice intravenously injected with PTX solution.