Development and validation of ratio spectra manipulation methods for the determination of etoricoxib and tramadol in binary mixtures.

Two simple and selective spectrophotometric methods, ratio difference and derivative ratio, were developed and validated for the simultaneous determination of etoricoxib and tramadol in binary mixtures and pharmaceutical formulations. The methods effectively resolved the sever spectral overlap of both drugs without prior separation. In the ratio difference method, amplitude differences between 294 and 239 nm for etoricoxib and 218 and 272 nm for tramadol showed excellent linearity. In the derivative ratio method, derivative amplitudes measured at 287 nm etoricoxib, and 229 nm tramadol provided high selectivity and sensitivity. The linear ranges were 2-23 µg/mL for etoricoxib and 3-40 µg/mL for tramadol, with correlation coefficients above 0.999. Both methods achieved recoveries between 98.78 and 101.09% and precision values (%RSD) below 2%. Statistical comparison with a reported HPLC method showed no significant difference. The proposed methods are accurate, cost-effective, and supported by AGREE-based greenness assessment, making them suitable for routine quality control of etoricoxib and tramadol formulations.