This study proposes a numerical approach based on spectroscopic data combined with partial least squares (PLS) multivariate analysis to simultaneously quantify quercetin and rifampicin in raw materials and liquisolid formulations. Spectral measurements were obtained for rifampicin and quercetin over a linear concentration range of 2–10 µg/ml for each compound. A total of 25 simulated mixtures were generated, including 16 calibration and 9 validation sets, using a wavelength interval of λ = 15 nm in 0.1 M hydrochloric acid and phosphate buffer at pH = 6.8, covering the spectral range of 200 to 630 nm. The suitability of the models was evaluated based on the root mean square errors (RMSE) obtained from the calibration and validation data sets. The analytical performance was further evaluated by comparing recovery percentages and relative prediction errors across different chemometric techniques. The results of the recovery analysis confirmed that this method effectively enabled pharmaceutical formulation without the interference of excipients. The proposed approach is rapid, user-friendly, and serves as a viable alternative to conventional analytical methods for formulation development and pharmaceutical quality control.
