Pharmacokinetic and tissue distribution of paclitaxel in rabbits assayed by LC-UV after intravenous administration of its novel liposomal formulation.

A simple, rapid and sensitive LC-UV method was developed and validated for the determination of paclitaxel (PTX) in rabbit plasma and tissues. A 2 mL aliquot of acetonitrile and 10 μL ammonium acetate (pH 5.0, 6 m) as extraction agents were used to markedly increase the extraction recoveries and greatly reduce the endogenous substances. The separation was achieved on a C18 column at 30 °C using an acetonitrile-ammonium acetate buffer (pH 5.0, 0.02 m; 55:45, v/v) at a flow rate of 1.0 mL/min; UV detection was used at 227 nm. Good linearity was obtained between 0.025 and 10,000 µg/mL for plasma and between 0.025-200,000 µg/g for tissue samples (r > 0.999). The limit of detection was 6 ng/mL in plasma, 8 ng/g in heart and 12.5 ng/g in other tissues. The limit of quantitation was 25 ng/mL in plasma and heart, 125 ng/g in other tissues. The intra- and inter-day assays of precision and accuracy for all bio-samples ranged from 1.38 to 9.60% and from 83.6 to 114.5%, respectively. The extraction recoveries ranged from 70.1 to 109.5%. Samples were stable during three freeze-thaw cycles or stored in a freezer at -20 °C for 30 days. The assay method was successfully applied to a study of the pharmacokinetics and tissue distribution of novel PTX lung targeting liposomes.
(Copyright © 2013 John Wiley & Sons, Ltd.)