Chemometrics-assisted spectrophotometric method for the simultaneous determination of phenylephrine hydrochloride, chlorpheniramine maleate and paracetamol

This study presents an eco-friendly, combined UV spectrophotometric method based on derivative ratio and second derivative for the simultaneous determination and quantification of phenylephrine HCl (PHE), chlorpheniramine maleate (CPM), and paracetamol (PAR) in pharmaceutical mixtures. In the derivative ratio method, sample spectra are divided by standardized spectra of the other components, followed by calculation of the first derivative. Analysis was performed at 226 nm for PHE, 271 nm for CPM, and 253 nm for PAR. The second derivative method uses second-order derivative absorption spectra, using zero-crossing points to selectively quantify each drug at 280.5 nm for PHE, 250.5 nm for CPM, and 245.5 nm for PAR. The linearity ranges were 0.1–30 μg/mL (PHE), 0.5–36 μg/mL (CPM), and 1–30 μg/mL (PAR) for the derivative ratio method; and 3–24 μg/mL (PHE), 1–15 μg/mL (CPM), and 1–14 μg/mL (PAR) for the second derivative method. The relative standard deviations were below 0.2 % for the derivative ratio method and below 3 % for the second derivative method. Method performances were benchmarked against a conventional HPLC-DAD technique and the eco-friendliness and greenness were evaluated using advanced assessment tools. The proposed method was effectively applied to commercial pharmaceutical formulations, confirming its reliability and environmental compatibility.