Stress degradation studies on cefpodoxime proxetil and development of a validated stability-indicating HPLC method

A simple, sensitive, specific, precise, and stability-indicating high-performance liquid chromatographic (HPLC) method for determination of cefpodoxime proxetil as bulk drug and as pharmaceutical formulation was developed and validated as per the International Conference on Harmonization (ICH) guidelines. An isocratic separation was achieved using a Phenomenex Luna C18 (250 mm × 4.6 mm i.d., 5 μm particle size) column with a flow rate of 1 mL min-1 and a UV detector to monitor the eluate at 254 nm. The mobile phase consisted of acetonitrile and 50 mM ammonium acetate pH 6 (pH was adjusted with o-phosphoric acid) in the ratio of 45:55 (υ/υ). The linear regression analysis data for the calibration plots showed good linear relationship with r2 = 0.9998 in the working concentration range of 1–80 μg mL-1 The LOD and LOQ were 0.17 and 0.5 μg mL-1, respectively. The drug was subjected to acid and alkali hydrolysis, oxidation, dry heat, wet heat treatment, and photodegradation. The standard drug peaks were well resolved from the degradation products’ peaks with significantly different retention time (tR), and the resolution factor for cefpodoxime proxetil was found to be greater than 1.7. As the method could effectively measure the drug in the presence of all degradation products and excipients expected to be present in the formulation, it can be employed as a specific stability-indicating method. Moreover, the proposed HPLC method was utilized to investigate the kinetics of the acidic and oxidative degradation processes at different temperatures. An Arrhenius plot was constructed and the apparent pseudo-first-order rate constant, half-life and activation energy were calculated.