A UFLC-MS/MS method coupled with one-step protein precipitation for determination of docetaxel in rat plasma: Comparative pharmacokinetic study of modified nanostructured lipid carrier

摘要

A rapid, simple and sensitive ultra fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) method coupled with one-step protein precipitation procedure has been developed and validated for the pharmacokinetic study of docetaxel in rat plasma to investigate the influence of polyethylene glycol (PEG) molecular weights (chain length) using in the modified formulations. Separation was achieved on a Venusil MP C18 column (100mm×2.1mm, 3.0μm) with a mobile phase consisting of methanol-water, and the total running time was 3.5min. The standard curve was linear over the range of 5-5000ng/mL, with lower limits of quantification (LLOQ) of 5ng/mL. The method was shown to be reliable and reproducible with intra-day precision below 10.7%, inter-day precision below 11.2%, accuracy within ±5.2%, and mean extraction recovery of 84.6-90.2%. The validated method was successfully applied to the comparative pharmacokinetic study of docetaxel in rat plasma after intravenous administration of docetaxel-loaded nanostructured lipid carrier modified by copolymers consisting of series of PEG molecular weights (2000, 4000, 10,000Da), respectively. The results indicated that PEG-4000 possessed a better and longer circulation effect, which made the modified formulation one of the promising suspensions for the delivery of docetaxel in cancer.