Develops validated, eco-friendly spectrophotometric techniques to selectively quantify entacapone in the presence of levodopa and carbidopa in pharmaceutical formulations without separation.

Provides practical, sustainable assays for routine quality control and manufacturing of entacapone-containing products but offers little mechanistic, translational, or therapeutic-discovery insight for Parkinson's disease research.

A selective and eco-friendly spectrophotometric approach was developed for the quantitative determination of entacapone (ENT) in the presence of its co-formulated drugs carbidopa (CAR) and levodopa (LEV) which exhibit severe spectral overlap. Three simple spectrophotometric methods; direct zero-order, factorized dual wavelength, and ratio subtraction coupled with constant multiplication techniques were optimized to enable effective resolution of the ENT spectrum without the need for prior separation or complex mathematical treatment. The proposed approaches demonstrated high selectivity toward ENT in laboratory-prepared mixtures and pharmaceutical dosage forms confirming the successful minimization of interference from CAR and LEV. The proposed methods showed excellent linearity over the concentration range of 1.5-14.0 µg/mL with a correlation coefficient (r) of 0.9998. The limit of detection (LOD) and limit of quantification (LOQ) were 0.226 µg/mL and 0.685 µg/mL, respectively confirming high sensitivity. The methods were validated according to international guidelines and proved suitable for routine quality control analysis. In addition, the environmental impact of the developed methods was comprehensively evaluated using multiple greenness assessment tools such as Analytical Eco-Scale, NEMI, GAPI, and AGREE tools confirming their excellent sustainability profile. In conclusion, the developed spectrophotometric methods provide a simple, accurate, precise, and green alternative for determining entacapone in the presence of spectral similar compounds without the need for separation or sophisticated instrumentation.