Advanced Biomedical Research (Jan 2018)
Development of a Rapid and Precise Reversed-phase High-performance Liquid Chromatography Method for Analysis of Docetaxel in Rat Plasma: Application in Single-dose Pharmacokinetic Studies of Folate-targeted Micelles Containing Docetaxel
Abstract
Background: A simple and sensitive reversed-phase high-performance liquid chromatography (HPLC) method based on liquid-liquid extraction was established and validated for determination of docetaxel (DTX) in plasma of rat. Materials and Methods: Samples were spiked with paclitaxel as the internal standard and the chromatographic separation was carried out using C18 HPLC column. The mobile phase consisted of a mixture of acetonitrile/water with the ratio of 60/40 v/v. The ultraviolet detector was operated at 230 nm, and the flow rate of mobile phase was 1 ml/min. The method was validated for linearity, precision, accuracy, recovery, and limit of quantification (LOQ). Then the method was applied to quantify DTX in the rat plasma after intravenous (IV) administration of the self-assembled micelles of folate-targeted Synpronic F127/cholesterol (FA-PF127-Chol) loaded with DTX and Taxotere® as the reference marketed solution of DTX. The blood samples were taken from the ophthalmic vein at predetermined time intervals after treatment. Results: Calibration curve was linear between the concentration ranges of 0.1–7.5 μg/ml with the relative standard deviation % and evaluating error % ranged from 2.263 to 15.53 and −12.75 to 12.7 for intra- and inter-day validity, respectively. The mean recovery of the drug after plasma extraction was 95.67 ± 0.99% for the concentration of 1 μg/ml. The LOQ and the limit of detection for DTX in serum were 100 ng/ml and 30 ng/ml, respectively. Conclusions: The results indicated that the developed method could be adopted for pharmacokinetic studies of DTX-loaded FA-PF127-Chol micelles and Taxotere® in rat.
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