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

A Quality by Design (QbD) systematic and analytical approach was used to develop a novel and sensitive Lenvatinib stability-indicating method. The ICH Q1A(R2) and Q3 guidelines were implemented to determine Lenvatinib degradation behavior under various environmental conditions. The QbD approach implementation has screening and optimization stages. The Placket-Burman design was used to assess primary parameters, and Response Surface Design (RSD) to optimize critical factors. The drug degradation was examined under different degradation conditions, including acidic, basic, oxidative, neutral, thermal, and photolytic conditions. Separation was achieved using a Shimadzu((R)) C18 column (250 mm x 4.6 mm, particle size 5 mu) with the mobile phase consisted of Acetonitrile: 10 mM ammonium acetate at pH 3.5 (39:61, v/v) at a flow rate 0.8 mL/min. The run time was 20 min and the wavelength used was 245 nm. The drug found sensitive toward acid and base hydrolysis, resulting in the generation of five degradation products. These products were successfully identified using 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 (R-2 = 0.9993). The greenness score of the analytical method was calculated, revealing that the developed method is environmentally friendly.