Abstract <p>Tovorafenib is an oral type II RAF(Rapidly Accelerated Fibrosarcoma) kinase inhibitor used for the treatment of pediatric low-grade glioma (pLGG) and solid tumours. The literature survey revealed that there is no reported eco-friendly stability indicating Reversed—phase liquid chromatographic method (RP-HPLC) method for the estimation of Tovorafenib. Hence, an eco-friendly stability-indicating RP-HPLC method for the quantification of Tovorafenib based on the principles of Analytical Quality by Design (AQbD) and Design of Experiment (DoE) concept has been developed. The AQbD approach was implemented by employing Response surface methodology and Central composite design by identifying the high- risk parameters and evaluating the risk using risk priority number (RPN) ranking and filtering based on the principles in accordance with ICHQ8, Q9, Q10 and Q14 guidelines. Complex MoGAPI (Complementary Modified Green Analytical Procedure)was used to assess the chromatographic method’s impact on the environment and demonstrated a final score of 94 with more green compartments and four yellow compartments proving its eco-friendliness. The optimized chromatographic method was validated according to ICH Q2(R2) guidelines. Tovorafenib was also subjected to Forced degradation studies as per ICHQ1(R2) guidelines and found to be degraded in acidic, alkaline, peroxide and hydrolytic environments and stable in photolytic, reduction and thermal conditions. The four degradation products identified were characterized by LC–MS/MS and their degradation pathways were proposed. The developed stability-indicating RP-HPLC method is less-time consuming, environmentally-friendly, economic, complies with the regulatory standards and can be recommended in routine analysis for the quantification of Tovorafenib.</p> Purpose <p>The main objective of the present work is to develop an eco-friendly stability-indicating RP- HPLC method based on Analytical Quality by Design (AQbD) and Design of Experiment (DoE) concept giving insight into the drug’s degradation behaviour. The present work is the first-ever reported method for the quantification of Tovorafenib as there is no previously reported stability-indicating eco-friendly method for the estimation of Tovorafenib.</p>