Application of Different Interval Variable Selectors for Quantification of Spectrally Overlapping Pharmaceuticals by Multivariate Calibration

The novel application of interval variable iterative space shrinkage approach iVISSA and partial least squares PLS calibration for quantification of three overlapping pharmaceuticals (Paracetamol, Guaifenesin, and Phenylephrine) is presented in this work. In addition to spectral overlapping, the drugs are available in the commercial tablet in varying proportions where Paracetamol and Guaifenesin are ۲۰ to ۵۰ times higher than Phenylephrine. Net analyte signal calculations indicated that pH has an high influence on drug overlapping, and the optimum pH was at ۱۲.۰, with a total overlapping ۵۷-۷۷% among solutes. To eliminate the influence of excipients on PLS calibration, all standard mixtures were prepared in a ۵% level of excipients. iVISSA resulted in the excellent prediction of Phenylephrine by selecting ۳۴ spectral data in which the solute was intensely absorbed. Analysis of commercial tablet (۲۵۰ mg Paracetamol, ۱۰۰ mg Guaifenesin, ۵ mg Phenylephrine) with the help of NAS revealed that GUA was predicted with high accuracy (۹۸.۴%) and precision (RSD ۳.۹) using the range ۲۲۵-۲۳۹ nm. For Phenylephrine, the selected intervals were ۲۰۰-۲۰۷, ۲۲۴-۲۲۵, ۲۳۲-۲۴۶, ۲۵۰-۲۵۴, ۲۶۳, ۲۶۷-۲۷۰, ۲۷۵, and ۲۷۸-۲۸۰ nm by iVISSA, which resulted in accurate quantification with high accuracy (۱۰۴.۳%) and precision (RSD ۰.۵). For Paracetamol, including the entire range (۲۰۰-۳۰۰ nm, ۱۰۱ points) was necessary for better PLS prediction while variables selection by NAS or iVISSA negatively affected PLS calibration for that drug. The accuracy and precision of the proposed method were validated against liquid chromatography and both methods were found statically comparable.

Keywords:

Interval variable selection methods , Spectral overlapping , PLS calibration , Pharmaceutical analysis