Comparative kinetic studies and pH-rate profiling of aniracetam degradation using validated stability-indicating RP-HPLC method

Abstract

Aniracetam is a cognitive enhancer drug that is susceptible to chemical degradation at room temperature. A validated stability-indicating RP-HPLC has been developed and used for studying the kinetics of aniracetam degradation processes and pH-rate profiling. Chromatographic separation of aniracetam and its degradation products was achieved on a C18 column (250 × 4.6 mm) with particle size 5 μm. The stationary phase surface silanol activity and hydrophobicity was evaluated by Galushko method then the mobile phase was optimized for the separation of intact drug from degradation products. Water-acetonitrile-methanol (50:25:25 v/v/v) was used as a mobile phase in isocratic mode with flow rate 1 mL/min. Aniracetam and its degradation products were monitored at 210 nm. Determination was carried out in the concentration range of 0.4–20 µg/mL with a detection limit of 0.21 µg/mL. A new behavior of aniracetam stability was concluded based on structural elucidation of degradation products by infra-red and mass spectrometry. Degradation kinetic parameters including the order of reaction, the rate constant, and half-life have been calculated. The study of the pH-rate profile was evaluated in the range of 3–10 pH units and it was found that aniracetam is stable in uncatalyzed degradation compared to the acid or base-catalyzed reaction. Good recoveries were obtained for aniracetam capsules and the proposed method validity was assessed by standard addition technique. Moreover, the results obtained were statistically compared with those obtained by the manufacturer method and therefore the proposed RP-HPLC method could be successfully used in quality control laboratories for the determination of aniracetam and detection of degradation products.