Quantitative Analysis of Active Compounds in a Three-Component Pharmaceutical Formulation Using Multivariate Calibration Methods

Abstract

A rapid, simple, and cost-effective spectrophotometric method combined with multivariate chemometric calibration was developed for the simultaneous determination of paracetamol (PRC), caffeine (CFN), and propyphenazone (PRPN) in a ternary pharmaceutical formulation without any prior separation step. The direct UV spectrophotometric analysis of these compounds is challenging due to the significant overlap of their absorption spectra within the 220-300 nm wavelength range, which limits the applicability of conventional methods. To overcome this issue, Partial Least Squares (PLS) and Principal Component Regression (PCR) techniques were applied to resolve the overlapping spectral data and enable accurate quantification. Calibration models were constructed using a training set of 35 laboratory-prepared mixtures in the concentration ranges of 3.0-16.0 µg/mL for PRC, 2.5-12.0 µg/mL for CFN, and 3.0-12.0 µg/mL for PRPN. The performance of the models was evaluated using statistical parameters such as SEC, SEP, and RMSEP, demonstrating strong predictive ability with low error values. Validation studies confirmed high accuracy (recoveries close to 100%) and precision (RSD < 3%), while robustness was verified through intra-and inter-day analyses. The method was successfully applied to commercial tablets, providing reliable and consistent results suitable for routine quality control applications.