Validation of an analytical method to determine stability in use of injectable Docetaxel-10 mg/mL

Abstract

Introduction: Docetaxel is a semi-synthetic drug with demonstrated antitumor activity approved for the treatment of patients with breast cancer, hormone- refractory prostate cancer and gastric cancer, locally advanced or metastatic. It is administered by slow intravenous infusion, so it is necessary to carry out a stability study in use to guarantee that the product is stable in these conditions.

Objective: Validate an analytical method to determine the stability in use of the injectable docetaxel-10 mg/mL.

Methods: The method was based on the separation of the active substance through an Apollo-C18 chromatographic column (5 μm) (250 x 4.6 mm), with ultraviolet detection at 232 nm. A mobile phase composed of a mixture of methanol: acetonitrile: water (44:26:30), with a flow rate of 1.5 mL/min, was used. The calibration curve was performed in the range of 0.125 mg/mL to 0.375 mg/mL.

Results: The method was linear, with a correlation coefficient equal to 1.0. Statistical evidence for intercept and slope was considered non-significant and significant, respectively. The coefficient of variation in the repeatability study was equal to 0.25% for the six replicates tested, while in the intermediate accuracy analyses the Fischer and Student's t tests were not significant. A recovery of 100.43% was obtained in the range of concentrations studied and the Cochran and Student's t tests were not significant. In the specificity study, no interference from additional peaks was observed near the retention time of the main product. The analytical method was linear, precise, accurate and specific in the range of concentrations studied.

Conclusions: The validated analytical method to determine the stability in use of the injectable docetaxel-10 mg/mL, turned out to be linear, precise, accurate and specific in the range of concentrations established between 0.125-0.375 mg/mL. The results allow to use the method for the realization of the stability study in use of the product in solutions of dextrose 5 % and sodium chloride 0.9 %.