Advanced chemometric methods for simultaneous quantitation of caffeine, codeine, paracetamol, and p-aminophenol in their quaternary mixture

Abstract

Abstract Two different multivariate techniques have been applied for the quantitative analysis of caffeine, codeine, paracetamol and p-aminophenol (PAP) in quaternary mixture, namely, Partial Least Squares (PLS-1) and Artificial Neural Networks (ANN). For suitable analysis, a calibration set of 25 mixtures with various ratios of the drugs and PAP impurity were established using a 4-factor 5-level experimental design. The most meaningful wavelengths for the chemometric models were chosen using Genetic Algorithm (GA) as a variable selection technique. By using an independent validation set, the validity of the proposed methods was evaluated. A comparative study was established between the three multivariate models (PLS-1, GA–PLS and GA–ANN). The comparison between the various models revealed that the GA–ANN model was superior at resolving the highly overlapped spectra of this quaternary combination. The drugs were successfully quantified in their pharmaceutical dosage form utilizing the GA–ANN models.