Comparison of Three RP-HPLC Methods for Analysis of Cefpodoxime Proxetil and Related Substances

A comparison of testing methods for analysis of cefpodoxime proxetil and its related substances was performed to determine which available analytical method was most appropriate for quality control. Three RP-HPLC methods are reviewed. They are adopted by Requirements for Antibiotic Products of Japan 1998 (Method 1), the United States Pharmacopoeia 28th (Method 2) and a method provided by a manufacture company (Method 3). Methods were compared in terms of specificity, stability of sample solution, sensitivity, precision, and robustness. Method 1 consisted only of water and methanol, eliminating possible degradations observed in phosphate and acetate buffers, and allowed baseline separation of cefpodoxime proxetil from its known related substances, including stereo and structural isomers, possible degradation compounds and by-products within 40 min, demonstrating more specificity and efficiency than Method 2. However, cefpodoxime proxetil dimer (open) could not be eluted within 60 min with Method 1. Method 3 gave partly similar results to those of Method 1 and also allowed the detection of cefpodoxime proxetil dimer (open). Results showed that Method 1 and Method 2 had some limitations for the impurity control. For chromatographic impurity control, Method 3 is the best choice.