Diode array detection for stability assessment and evaluation of degradation kinetics of newly introduced sacubitril in its supramolecular complex (LCZ696) with valsartan

Abstract

ABSTRACTA newly FDA-approved heart failure therapy (LCZ696, supramolecular complex of sacubitril (SAC) and valsartan (VAL), Entresto™) is analyzed with a stability indicating HPLC–DAD method. For the newly introduced drug, SAC, there is no sufficient information about its stability under various stress conditions. The proposed chromatographic method was applied to the kinetic investigation of the acidic, alkaline, and oxidative degradation of SAC with the estimation of its activation energy and half-life at room temperature by the aid of Arrhenius plots. Kinetic investigation was conducted using either different strengths of HCl, NaOH, and H2O2 at one selected temperature or different temperature degrees at one selected reagent strength, for the acidic, alkaline, and oxidative stress conditions. It was found that the pseudo-first-order kinetics was followed at each case. The half-lives at room temperature using 0.1 M HCl, 0.01 M NaOH, and 15% H2O2 were found to be 20.50, 2.76, and 51.58 hr. The chromatographic method was achieved using Zorbax Eclipse plus-C18 (4.6 × 250 mm, 5 µm) with isocratic elution of mobile phase composed of acetonitrile and 0.025 M phosphate buffer (pH3) in a ratio of 60:40 (v/v).