Green Easily Implemented Spectrophotometric Methods for Concurrent Determination of Ephedrine Hydrochloride and Naphazoline Nitrate in Nasal Preparations Containing Methylparaben.

The article focuses on the development and validation of green, cost-effective spectrophotometric methods for the simultaneous determination of ephedrine hydrochloride (EPH) and naphazoline nitrate (NAP) in nasal preparations containing methylparaben (MET) as a preservative. The authors introduced a derivative dual-wavelength method alongside successive derivative subtraction and chemometric techniques (principal components regression and partial least squares) to resolve overlapping spectra of the ternary mixture. These methods comply with International Conference on Harmonization (ICH) guidelines for accuracy, precision, selectivity, and linearity, and demonstrate limits of detection suitable for pharmaceutical analysis. Compared to existing chromatographic methods, the proposed approaches offer advantages in simplicity, cost, and environmental impact, as confirmed by greenness assessment tools including Eco-scale, GAPI, and AGREE. The methods were successfully applied to both synthetic mixtures and a marketed nasal spray formulation, showing no significant difference from established HPLC techniques.