Quantification of cabazitaxel, its metabolite docetaxel and the determination of the demethylated metabolites RPR112698 and RPR123142 as docetaxel equivalents in human plasma by liquid chromatography-tandem mass spectrometry.

Abstract

We present a sensitive validated LC-MS/MS assay for the simultaneous determination of cabazitaxel and docetaxel in human plasma, with calibration ranges of 1.0-150 ng/mL for cabazitaxel and 0.1-15 ng/mL for docetaxel. Sample pretreatment consisted of liquid-liquid extraction with tert-butyl methyl ether. Chromatographic separation was achieved on a Zorbax Extend C18 column using a gradient mixture of 10mM ammonium hydroxide and methanol. Mass detection was carried out by turbo ion spray ionization in positive ion multiple reaction monitoring mode. All inter-day accuracies and precisions were within ±15% of the nominal value and within ±20% at the lower limit of quantitation. Demethylations of cabazitaxel yielding the metabolites RPR112698 and RPR123142 were monitored semi-quantitatively and quantified as ng docetaxel equivalents. Plasma samples of a prostate cancer patient treated with cabazitaxel were analyzed to demonstrate the usefulness of the presented assay for clinical drug monitoring. In conclusion, this method can be applied to support clinical pharmacokinetic studies with the novel anticancer drug cabazitaxel.