Evaluation of multivariate calibration models with different pre-processing and processing algorithms for a novel resolution and quantitation of spectrally overlapped quaternary mixture in syrup

•Resolve a quaternary mixture with extremely overlapped spectra•Multivariate calibration methods: CRACLS, PLS, CWT-PLS•Novel hybridization between CWT and PLS•Comparative study between PLS and CWT-PLS.•Methods were applied in bulk powder and pharmaceutical formulation.

A novel approach for the resolution and quantitation of severely overlapped quaternary mixture of carbinoxamine maleate (CAR), pholcodine (PHL), ephedrine hydrochloride (EPH) and sunset yellow (SUN) in syrup was demonstrated utilizing different spectrophotometric assisted multivariate calibration methods. The applied methods have used different processing and pre-processing algorithms. The proposed methods were partial least squares (PLS), concentration residuals augmented classical least squares (CRACLS), and a novel method; continuous wavelet transforms coupled with partial least squares (CWT-PLS). These methods were applied to a training set in the concentration ranges of 40–100 μg/mL, 40–160 μg/mL, 100–500 μg/mL and 8–24 μg/mL for the four components, respectively. The utilized methods have not required any preliminary separation step or chemical pretreatment. The validity of the methods was evaluated by an external validation set. The selectivity of the developed methods was demonstrated by analyzing the drugs in their combined pharmaceutical formulation without any interference from additives. The obtained results were statistically compared with the official and reported methods where no significant difference was observed regarding both accuracy and precision.

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