THE DETERMINATION OF ALENDRONATE SODIUM IN MICROPARTICULAR SYSTEMS BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY

Sibel ŞAMDANCIOĞLU*, Sema ÇALIŞ*,º, Sedef KIR**, Murat ŞUMNU*

* Hacettepe University, Faculty of Pharmacy Department of Pharmaceutical Technology, 06100 Sıhhiye, Ankara, TURKEY.
** Hacettepe University, Faculty of Pharmacy Department of Analytical Chemistry, 06100 Sıhhiye, Ankara, TURKEY.
º Corresponding author e-mail: scalis@hacettepe.edu.tr
• web site: http://yunus.hacettepe.edu.tr/~scalis

Summary:
Alendronate sodium (AS) is an aminobisphosphonate that inhibits especially the osteoclast-related bone resorption. In orthopaedics, in order to make the total joint prostheses stay in the body for a long time without causing bone tissue loss, microparticular system formulations loaded with AS for implantation were prepared to be applied locally on those regions to prevent osteolysis. The purpose of this study was to apply a sensitive and reliable high performance liquid chromatography (HPLC) method for the determination of drug content in microparticular system formulations and the amount of drug present in the release medium. A validated pre-column HPLC method using 9-fluorenylmethyl chloroformate (FMOC) derivatization was used to determine the amount of AS from the microparticular systems prepared using different polymers. A reverse phase (PRP-I) column (10 ?m particle size, 250?4.1 mm, i.d. (internal diameter), Hamilton, NV, USA) was used. The mobile phase, a mixture of 0.05 M sodium citrate and sodium phosphate buffer (pH 8)-acetonitrile-methanol (75:20:5, v/v/v) was delivered at flow rate of 1.0 ml/min at room temperature. Parameters examined for the analytical method validation were linearity, accuracy, precision, sensitivity, selectivity and stability. Calibration curve of AS was fount to be linear over a concentration range of 0.5-20 ?g/ml (R²:0.999). The precision and accuracy of the method were found to be lower than 2% by statistical evaluation, and AS was found to be stable during release studies. This HPLC method was applied successfully to the analysis of the drug in microparticular systems. It was found that the amount of drug loaded in microspheres and the amount of released drug into the medium during in vitro release studies were determined precisely by this HPCL method.

Keywords:
Alendronate sodium, HPLC, Method validation, Microspheres, Beads.