Eco-Friendly Stability Indicating HPLC Method for Estimation of Elbasvir and Grazoprevir by Quality by Design Approach

Abstract

Introduction: The pharmaceutical industry faces a significant problem as a result of the worldwide requirement to modify processes in order to comply with the green analytical chemistry (GAC) requirements. An enormous amount of organic hazardous waste is produced by high-performance liquid chromatography (HPLC), one of the methods employed the most frequently at different stages in the pharmaceutical sector. Aim: To develop analytical quality by design-aided stability indicating green high-performance liquid chromatography (HPLC) method for estimation of Elbasvir and Grazoprevir in a dosage form. Material and Methods: The critical chromatographic factors were the % of ethanol in the mobile phase, flow rate, and their overall effect on the responses like asymmetry, theoretical plates, and resolution were studied to optimize the method. Green analytical chemistry (GAC) has mainly focused on developing analytical methods that are safe for the environment. Therefore, it is imperative that the GAC principles be applied in pharmacological analysis. A rotatable central composite design was employed, and the optimized conditions for chromatographic separation were made with a run time of 5 minutes using Zorbax C18 column (4.6× 150 mm, 5 µm) with 0.1% Trifluoroacetic acid and ethanol (40:60 v/v) as components of a mobile phase, flowing at a rate of 1.0 ml/minute. Photodiode array detection was carried out at 253 nm. Results: The retention time was 1.8 min for EBS and 2.84 min for GZP. According to the ICH guidelines, the proposed method was validated and stress studies revealed that Elbasvir and Grazoprevir are prone to acidic, basic, and oxidation stress conditions. An analytical eco-scale score evaluated the greenness profile and a software-based evaluation. Conclusion: The developed HPLC method is eco-friendly and shall be adopted in the routine quality control of Elbasvir and Grazoprevir in a tablet dosage form.