Amoxapine (AMX), a tricyclic antidepressant, is widely used in the management of depression and other neuropsychiatric disorders. However, the robust, sustainable, stability-indicating, and optimised method for AMX analysis is still lacking. Existing analytical methods are often hampered by excessive solvent consumption, which is a consequence of long run times. To address these limitations, this study implemented a sustainability-integrated Analytical Quality-by-Design (AQbD) framework to develop the first rapid, stability-indicating UPLC-PDA method for the AMX. A Box–Behnken response surface design was implemented to optimize high-throughput separation on a C18 column in an ultra-short runtime. Compared with previously reported conventional HPLC methods, this approach achieved a 75% reduction in analysis time and a 95% reduction in solvent usage. The developed method demonstrated high sensitivity, robustness, and excellent resolution during stability studies. Forced degradation studies confirmed its stability-indicating capability through effective resolution and peak-purity analysis. The method was evaluated using multiple green analytical assessment tools (e.g., Analytical Eco-Scale and AGREE), yielding a superior score of 0.81 and a significantly reduced carbon footprint (0.0453 kg CO 2 per analysis). The method is suitable for routine quality control and stability monitoring, providing a robust and environmentally responsible framework for pharmaceutical analysis.
Labhade et al. (2026) studied this question.