THREE-WAY DATA ANALYSIS OF COPPER-PARACETAMOL COMPLEX FORMATION FOR THE QUANTIFICATION OF PARACETAMOL IN PHARMACEUTICAL MATRICES

Abstract

We present a chemometric strategy to study complex formation reactions using parallel factor analysis (PARAFAC) of three-way spectral data.UV spectra of PAR, CuSO4, and their complex were recorded at five different pH levels. Reorganizing the spectra produced a wavelength & times; sample & times; pH array, to be decomposed by PARAFAC into spectral, pH, and concentration modes. This strategy achieved the resolution of contributing species and their profiles without requiring advanced instrumentation. PAR quantification was achieved using the relative concentration mode of the PARAFAC model. The calibration curve showed linearity in the range of 1.10x10-5 M-8.90x10-5M, and standard-addition validation yielded recoveries of 96.70-99.00% for tablets and 96.48-99.67% for syrups. Crucially, this strategy achieved accurate quantification of PAR in syrup formulation even with uncalibrated interferences in syrup matrix. The application of PARAFAC to the pH-dependent UV dataset acquired according to Job's method revealed a 1:1 stoichiometric ratio between PAR and Cu2+. Overall, the results demonstrate that three-way decomposition of pH-resolved UV measurements offers a practical and reliable alternative for studying Cu-PAR complex formation and quantifying PAR in different pharmaceutical matrices. To the best of our knowledge, this is the first PARAFAC application to study PAR-Cu complex formation for accurate quantification of PAR in the presence of uncalibrated interferences.