Robust RP-HPLC Method With Forced Degradation Studies for the Simultaneous Quantification of Efonidipine HCL Ethanolate and Metoprolol Succinate

Background: Efonidipine HCl Ethanolate and Metoprolol Succinate combination, exhibit a synergistic effect in mitigating thrombocytopenia. A highly reliable and stability-indicating analytical method was meticulously developed and rigorously validated for the concurrent quantification of these compounds in their bulk form. The analysis used a Shimpack C18 column (250 × 4.6 mm, 5 µm) with isocratic elution. The optimized mobile phase consisted of acetonitrile (ACN), Methanol, and phosphate buffer (pH 3.5) in a 65:20:15 (v/v/v) ratio, delivered at a flow rate of 1.0 mL/min. Detection was performed at 225 nm using a photodiode array (PDA) detector. The method was validated per ICH Q2 (R1) guidelines, and forced degradation studies were conducted under acidic (1N HCl), alkaline (1N NaOH), oxidative (3% H₂O₂), thermal (110°C for 3 hours), and photolytic (UV light exposure) conditions. Results: Efonidipine (EFO) and Metoprolol (MET) were eluted at retention times of 7.17 and 2.77 minutes, respectively. The method demonstrated linearity for EFO (20–120 µg/mL, r² = 0.9981) and MET (12.5–75 µg/mL, r² = 0.9961). The average recovery rates for Efonidipine HCl Ethanolate were 98.98%, 101.65%, and 98.65%, while for Metoprolol Succinate, they were 100.40%, 98.21%, and 101.6%, assessed at three concentration levels. Precision studies, including method repeatability and intermediate precision, met acceptance criteria. The method exhibited high accuracy, precision, robustness, sensitivity, and efficiency. Stability studies revealed that both drugs remained stable under thermal and photolytic conditions but showed significant degradation under acidic, alkaline, and oxidative stress. Conclusion The stability-indicating method is reliable and ideal for routine analysis and stability studies in quality control lab.