Advanced eco-friendly spectrophotometric analysis for Nebivolol, Valsartan, and related impurity with comprehensive environmental impact assessment.

At present, one of the main priorities for analysts is creating more sustainable and environmentally friendly methods for pharmaceutical analysis. In this context, three innovative spectrophotometric techniques, using tri-colored (green, blue, and white), were optimized and developed to simultaneously assess two antihypertensive drugs, Nebivolol hydrochloride (NEB) and Valsartan (VAL), in the presence of synthetic precursor impurity of Valsartan (Valsartan Desvaleryl, VAL-D), which is the main acidic degradation product. The methods employed, including the double divisor-ratio spectra derivative spectrophotometric method, the dual-wavelength in ratio spectrum method, and the H-point derivative ratio method, displayed a good linear range of 2.5-70 µg/mL, 10-50 µg/mL, and 10-70 µg/mL for NEB, VAL, and VAL-D, respectively. Assessment of greenness was implemented to the established methods using the analytical Eco-Scale scoring, analytical greenness metric (AGREE), and the green analytical process index (GAPI). The concepts of blueness assessment using the recently introduced Blue Applicability Grade Index (BAGI tool) and whiteness assessment using the Red Green Blue 12 (RGB 12 tool) were also applied. The proposed methods were validated as per ICH guidelines and verified to be accurate. Statistical analysis was performed to ensure the validity of methods concerning published methods.