Identification and Structural Characterization of Forced Degradation Impurities of Sacubitril by HRMS – Development and Validation of a Stability indicating RP-HPLC method
According to current regulatory guidelines, a stability‐indicating method has been developed to determine the impurities in the sacubitril and valsartan tablets dosage forms and perform robustness study using the design of the experiments approach. The present study was initiated to understand quality target product profile, analytical target profile and risk assessment for method variables that affect the method response. An RP‐HPLC system equipped with Phenomenex Gemini‐NX C18 column (150 mm x 4.6mm, 3μ), and PDA detector. A gradient mobile phase was used in this research work. The detection was made 254 nm; the flow rate was 1.5ml/min, and the column temperature was maintained at 30°C. The proposed method was validated as per ICH Q2 (R1) guidelines. The coefficient of correlation of >0.999 for all impurities. The limit of detection and quantification were evaluated for sacubitril, valsartan and all impurities. The precision and accuracy were obtained for sacubitril, valsartan and their related impurities. Intra ‐ and inter‐day RSD values were lower than 10.0%, and recoveries of impurity varied between 90.0 and 115.0 %. Based on the validation results, the proposed DoE method can estimate sacubitril and valsartan impurities in the finished dosage form.