Advancing Quality and Environmental Responsibility: A Stability-Indicating LC Method Development for Lenvatinib through QbD and Green Chemistry

Abstract

Abstract A Quality by Design (QbD) technique that was systematic and analytical was utilized to create and confirm a novel and sensitive stability-indicating method of Lenvatinib via the HPLC method. To comply with ICH Q1(A) guidelines, a study was conducted to determine the degradation behavior of Lenvatinib under various environmental conditions. The QbD approach involved screening and optimization, which included using Placket Burman to assess primary parameters, and Response Surface Design (RSD) to optimize critical factors. The degradation was examined under different degradation conditions, including acidic, basic, oxidative, neutral, thermal, and photolytic, and was separated using a Shimadzu® C18 column (250 mm x 4.6 mm, particle size 5 µ). The mobile phase consisted of a concentration of Acetonitrile: 10 mM ammonium acetate having pH 3.5 (39:61, v/v) at a flow rate of 0.8 mL/min, 20 min run time, and 245 nm wavelength. The drug was particularly sensitive towards acidic and basic hydrolysis stress conditions, which generated a total of five degradant products that were successfully identified with the optimized LC-MS compatible analytical method. The optimized method was found to be sensitive, reproducible, specific, and robust, with a linearity range of 10 to 60 mg/mL and a correlation coefficient (R2 = 0.9993). The greenness score of the analytical method was calculated, and it was observed that the developed method was environmentally friendly.