Chemometric quality assessment of Paracetamol and Phenylephrine Hydrochloride with Paracetamol impurities; comparative UV-spectrophotometric implementation of four predictive models

[Display omitted] •Smart and advanced chemometric approaches for determination of Paracetamol and Phenylephrine HCl in presence of Paracetamol impurities.•Comparative study between PCR, PLS, ANN and MCR-ALS models as multivariate calibrations.•Detection and quantification of Paracetamol impurities namely, P-Aminophenol, P-Nitrophenol, Acetanilide and P-Chloroacetanilide due to their toxicity.•The proposed models are effectively used for determination of the cited drugs in dosage form without any preliminary separation step. Spectrophotometric data analysis using multivariate approaches has many useful applications. One of these applications is the analysis of active ingredients in presence of impurities. Four chemometric-assisted spectrophotometric methods, namely, principal component regression (PCR), partial least-squares (PLS), artificial neural networks (ANN) and multivariate curve resolution-alternating least squares (MCR-ALS) were proposed and validated. The developed chemometric methods were compared to resolve the severely overlapped spectrum of Paracetamol (PAR) and Phenylephrine HCl (PHE) along with PAR impurities namely, P-Aminophenol (PAP), P-Nitrophenol (PNP), Acetanilide (ACT) and P-Chloroacetanilide (CAC). The four multivariate calibration methods succeeded in simultaneous determination of PAR and PHE with further quantification of PAR impurities. So, the proposed methods could be used with no need of any separation step and successfully applied for pharmaceutical formulation analysis. Furthermore, statistical comparison between the results obtained by the proposed chemometric methods and the official ones showed no significant differences.