A rapid analytical method for the quantification of paclitaxel in rat plasma and brain tissue by high-performance liquid chromatography and tandem mass spectrometry

RATIONALE: Paclitaxel, an antitumor agent for the treatment of several types of cancers, has recently been reported to cause impaired cognitive function and neuropathic pain in humans. To assess the effects of paclitaxel on the central nervous system, a sensitive and accurate method is required to quantify paclitaxel concentrations in plasma and brain tissue obtained from rodents receiving paclitaxel. METHODS: The biological samples were prepared by liquid-liquid extraction and separated by a 3.5min reversed-phase liquid chromatography (RPLC) method using a BDS Hypersil C8 column under isocratic conditions. Paclitaxel was quantified using multiple reaction monitoring (MRM) with a triple quadrupole tandem mass spectrometer working in the positive electrospray ionization (ESI+) mode. A stable isotope labeled analogue of paclitaxel was used as the internal standard (IS). RESULTS: The method was validated to be precise and accurate within the dynamic range of 0.5-100ng/mL based on 100L plasma and 1.5-300ng/g based on 33mg of brain tissue in homogenate. This method was applied to samples from 2mg/kg intravenously dosed rats. The plasma concentrations were observed to be 26.62 +/- 8.93ng/mL and brain concentrations 11.08 +/- 4.18ng/g when measured 4h post-dose. CONCLUSIONS: This rapid LC/MS/MS method was validated to be sensitive, specific, precise and accurate for the quantification of paclitaxel in rat plasma and brain tissue homogenate. Application of the method to study samples provided sufficient proof of blood-brain barrier penetration of paclitaxel, allowing further investigation of its influence on the central nervous system. Copyright (c) 2013 John Wiley & Sons, Ltd.