LC–MS/MS quantitative analysis of paclitaxel and its major metabolites in serum, plasma and tissue from women with ovarian cancer after intraperitoneal chemotherapy

Abstract

A method for determination of the antineoplastic drug paclitaxel and its main metabolites (viz. 6α-hydroxypaclitaxel and p-3′-hydroxypaclitaxel) at the sub-ng/ml level is here presented. Sample preparation consisted of a liquid–liquid extraction step for cleanup and preconcentration of the target analytes prior to chromatographic analysis by tandem mass spectrometry detection (LC–ESI-MS/MS). The determination step was optimized by selected reaction monitoring (SRM) mode for highly selective identification and sensitive quantitation of paclitaxel and its metabolites in human serum, plasma and tissue. The detection limits were in the range 0.03–0.15ng/ml for serum and 0.07–0.62ng/g for tissue, with intra-day variability range from 0.5 to 2.7%, expressed as relative standard deviation. The method was applied to determine paclitaxel and its metabolites in serum and tissue from 13 women suffering from ovarian peritoneal carcinomatosis, after hyperthermic intraperitoneal intraoperative chemotherapy (HIPEC) treatment. The method reported here can be considered a suited tool to monitor the concentration of this drug in patients subjected to HIPEC as strategy to evaluate the toxicity and efficiency of this treatment.