Optimization of HPLC methods for the development of quality control methods of combined powder formulations with paracetamol, phenylephrine hydrochloride, pheniramine maleate

Abstract

Our main goal was to optimize HPLC methods for the determination of a combined powder containing paracetamol, phenylephrine hydrochloride, and pheniramine maleate based on the indicators «Quantitative determination», «Uniformity of dosage units», and «4-aminophenol». Precise HPLC methods were developed for determining paracetamol, phenylephrine hydrochloride, pheniramine maleate, and the impurity of paracetamol (4-aminophenol). The method was optimized by selecting the chromatographic column and gradient elution to balance component separation and chromatographic time. Separation was achieved using a diode array detector at 273 nm («Quantitative determination», «Uniformity of dosage units») and 225 nm (4-aminophenol) with a gradient mobile phase consisting of a 1.1 g/L sodium octanesulfonate solution (pH 3.2), methanol, and a chromatographic column Zorbax SB-Aq. The method showed a linear response in the range of 160–360 µg/mL for paracetamol, 5–11 µg/mL for phenylephrine hydrochloride, and 10–22 µg/mL for pheniramine maleate. The optimized method, validated according to ICH guidelines, reduced run times to 20 min for impurity analysis and 10 min for active ingredients, which is twice as fast as the official pharmacopeial method. The developed methods were successfully applied for the quality control of this powder.