A rapid and stability-indicating, reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed for the determination of Sacubitril impurities in Sacubitril and Valsartan Microsphere Dosage form. Sacubitril, an antihypertensive drug is used in the treatment of heart failure with the combination of valsartan. There is no literature and official methods for this combination of drugs in the microsphere dosage form. Hence developed a related substances method for Sacubitril and Valsartan Microsphere Dosage form. Sacubitril impurities separation from Sacubitril, valsartan microsphere matrix was achieved on waters X Bridge C18 column (250 mm x 4.6 mm x 5 μm) gradient elution mode using 10 mM Disodium Hydrogen Phosphate Buffer and acetonitrile as mobile phase and at a flow rate of 1.0 ml/min. Detection was done at 278nm using a UV detector. The same method will be validated in line with ICH Q2 (R1) Guidelines and ICH Q3B (R2) Guidelines. Following parameters were considered for analytical method validation unspecified degradation products System suitability, Specificity (Blank, Placebo Interference, Forced degradation), Limit of detection, Limit of quantification, Linearity, Precision (System precision, Method precision, Intermediate precision), Accuracy, Range, solution stability and Robustness. Forced degradation studies were performed on samples using acid (0.5 N hydrochloric acid), base (0.5 N sodium hydroxide), oxidation (5% v/v hydrogen peroxide), heat (60 °C), UV light (Exposed to Not less than 1.2 million lux hours/and 200 WH/m2). Degradation of the drug substance was observed in acid, base hydrolysis and Peroxide. By using this developed LC method, stressed samples were analyzed and the mass balance was found to be close to 99.5%, thus it confirms the stability-indicating power. Validation acceptance criteria were met in all cases. This method was used successfully for the determination of Sacubitril Impurities in Sacubitril and Valsartan Microsphere Dosage form.

RP-HPLC, stability-indicating, Sacubitril, Microsphere, Forced degradation study