STABILITY-INDICATING HIGH PERFORMANCE LIQUID CHROMATOGRAPHIC DETERMINATION OF FLUCONAZOLE IN THE PRESENCE OF ITS OXIDATIVE DEGRADATION PRODUCT - KINETIC AND STRESS STUDY

Abstract

A simple, specific, accurate, and stability-indicating high performance liquid chromatographic method (HPLC) method has been established for analysis of fluconazole (FLZ) in the presence of its degradation products generated in the stress degradation study. FLZ was subjected to stress conditions of acid, alkali, and neutral hydrolysis, oxidation, photolysis, and thermal decomposition. Extensive degradation was found to occur in oxidative medium under thermal stress. Successful separation of drug from degradation products was achieved on a C-18 column using phosphoric acid 0.5% v/v: acetonitrile (80:20% v/v) as the mobile phase. The flow rate was 1.5 mL min−1 and the detector was set at 261 nm. The retention times of FLZ and its main oxidative degradation product were found to be 5.389 min and 2.729 min, respectively. Linearity was established for fluconazole in the range of 0.5–50 µg/ml. The percentage recovery of fluconazole was found to be 99.91 ± 0.74. Because the method effectively separates fluconazole from its oxidative degradation products, it can be used as stability-indicating method. The proposed method was also used to study the kinetics of fluconazole oxidative degradation that was found to follow a zero-order reaction. The t1/2 was 21.66 min while k (reaction rate constant) was 2.91 × 10−8 mole/min.