Eco-conscious AQbD-guided stability-indicating RP-UPLC method for analysing Tovorafenib in bulk and dosage forms

Résumé fourni par la source

Tovorafenib is a type II RAF inhibitor recently approved by the FDA for relapsed or refractory paediatric low-grade glioma in children aged 6 months and older with BRAF fusions or V600E mutations, owing to its strong central nervous system penetration and absence of paradoxical MAPK pathway activation observed with type I inhibitors. This study developed and validated a fast, robust, and environmentally friendly reversed-phase ultra-performance liquid chromatography method for Tovorafenib quantification, employing ICH Q14 development, ICH Q2(R1) validation, and assimilating Analytical Quality by Design and green analytical chemistry principles. Chromatographic analysis was performed using a Waters Acquity UPLC BEH C18 column and 0.01 N Na₂HPO₄ in water: methanol (62:38 v/v) as the mobile phase at 0.29 ml/min, with PDA detection at 292 nm. The optimized approach exhibited excellent linearity (r² = 0.9997) and reproducibility (low %RSD). Forced degradation studies demonstrated Tovorafenib stability under most conditions, except during acid hydrolysis. Assessment with green chemistry tools yielded favourable eco-scores (ComplexMoGAPI 90, AGREE 0.61, BAGI 70, RAPI 92.5, EVG Q2, and RGBfast 97.5%). This validated RP-UPLC procedure offers reliable, sensitive, and sustainable Tovorafenib analysis, supporting both efficient pharmaceutical quality control and environmental sustainability.