A green validated HPLC-UV Method for determining and quantifying pholcodine, paracetamol, and pseudoephedrine in laboratory-prepared mixtures and their FDC capsule

Abstract

A validated technique has been developed for the sequential determination of pholcodine, paracetamol, and pseudoephedrine. This method allows for their separation either in different ratios within a ternary mixture or in their fixed-dose combination (FDC) using HPLC. The chromatographic conditions involved the utilization of an X-select C₁₈ column (5µ, 4.6 × 150 mm) and a mobile phase consisting of 0.05 M KH₂PO₄: Methanol (75:25, v/v), with orthophosphoric acid added to adjust the pH to 2.6. The separation was conducted at a 1.2 ml/min flow rate, while a UV detector was set at a wavelength of 206 nm to monitor the process. The three drugs were successfully eluted with retention times of 0.8, 1.9, and 3.0 min for pholcodine, paracetamol, and pseudoephedrine respectively providing fast analysis times.

The method exhibited linearity for pholcodine, paracetamol, and pseudoephedrine over concentration ranges of 12–200 µg/ml, 5–100 µg/ml, and 30–200 µg/ml, respectively. It was accurate, reliable, and precise (RSD < 2 %). This proposed methodology was effectively implemented to quantify the concentration of pholcodine, pseudoephedrine, and paracetamol in freshly prepared mixtures and pharmaceutical dosage forms. Furthermore, the method's environmental impact was assessed using five different tools, demonstrating low hazard levels to the environment, and promoting its environmental friendliness compared to the reported method.