Impurity Profiling of Sacubitril Valsartan Complext Using LC-MS Compatible Analytical Method

Abstract

Sacubitril and Valsartan (SAC/ VAL) complex is a novel-acting drug combination that is highly popular in the treatment of heart failure. In the present work, the LC-MS compatible stability indicating assay method was developed and validated for the simultaneous estimation of SAC/ VAL in presence of their process-related impurities and degradation products. The chromatographic separation was achieved on BDS Hypersil C8, (150 x 4.6) mm; 5 μm at 30° C. The peaks of SAC, VAL and their seven known impurities were well separated using 0.5 % trifluoracetic acid (TFA) in water as mobile phase A and 0.5 % TFA in acetonitrile as mobile phase B in a gradient mode. The analytes were monitored in the range of 200-400 nm using a photo diode array (PDA) detector. The method was validated as per ICH Q2 (R1) guideline and all the validation parameters were found to be the in-acceptance criteria. The forced degradation study for SAC/ VAL showed that the drug was susceptible to degrade under acidic and alkaline hydrolytic and oxidative stress conditions. The six major degradation products were found and further identified by LC-MS study. The LC-MS study revealed that two degradation products found at RRT 0.652 and 0.912 were known as DES-VAL and DIA- SAC. The four degradation products were found unknown which can be further identified using LC-MS/MS.