RP-HPLC Method Development for Impurity Profiling of Perindopril and Indapamide FDC Using Risk-Based AQbD Approach and Spectroscopic Characterization of Impurities

Pharmaceutical impurities resulting from degradation, synthesis, or excipient interactions can severely impact drug safety and efficacy. Consequently, this project centers on developing a risk-based analytical quality-by-design (RB-AQbD) HPLC method for impurity profiling of the two common antihypertensives, Perindopril and Indapamide, present in combination (FDC) formulations. Method development was performed for the separation and quantification of the drugs along with their degradation products; subsequent isolation and characterization of the impurities were achieved using IR, LC-MS/MS, and NMR spectroscopy. The optimized HPLC method resolved Perindopril (tR: 3.5 min), Indapamide (tR: 7.3 min), and their corresponding major degradation products. Isolation of the impurities was done via preparative LC, and structure characterization was performed. Thus, this study contributes towards the quality control and regulatory compliance of Perindopril and Indapamide FDC formulations.