Development and validation of a stability indicating UHPLC method for Sacubitril/Valsartan complex in the presence of impurities and degradation products

ABSTRACT

Sacubitril/Valsartan (SAC/VAL) is a combination drug used for the treatment of heart failure. In the present work,novel and rapid, sensitive, specific, and robust ultra high-performance liquid chromatography method was developedand validated for the simultaneous estimation of SAC/VAL in presence of their seven related impurities anddegradation products. The chromatographic separation was achieved on Accucore XL C8, (100 × 4.6) mm; 3 μmreverse phase column maintained at 30°C. The peaks were eluted using tetrahydrofuran (THF) and 0.1% perchloricacid in water (892, %v/v) as a mobile phase A and THFwateracetonitrile (51580, %v/v/v) as mobile phase B in agradient mode. The flow rate was set at 0.6 ml/minute and the analytes were monitored in the range of 200–400 nmusing a Photo Diode Array (PDA) detector for 21 minutes run time. The method was validated as per ICH Q2 (R1)guideline and all the validation parameters were found within the acceptance criteria. The forced degradation studyfor SAC/VAL showed that the drugs were prone to acidic, alkaline, and neutral hydrolytic as well as oxidative stressconditions. All the degradation products were separated from each other, SAC/VAL and their impurities showing thestability indicating power of the method. The newly developed method can be used for estimation of assay and relatedsubstances from bulk or their finished products with good efficiency.