Highly sensitive sequential injection determination of p-aminophenol in paracetamol formulations with 18-molybdodiphosphate heteropoly anion based on elimination of Schlieren effect

► Determination of p-aminophenol with 18-molybdodiphosphate by SIA method. ► A new strategy has been proposed to reduce the Schlieren effect. ► Careful matching of the reagent and buffer concentrations decreases Schlieren effect. ► Using new strategy allowed to improve sensitivity by one order of magnitude. ► Amount as low as 0.001% of p-aminophenol can be determined in paracetamol tablets. A highly sensitive, precise and automated method using sequential injection analysis to assay quantitatively low levels of the p-aminophenol (PAP) in paracetamol formulations has been developed. A solution containing PAP and paracetamol is injected into an acetate buffer carrier stream and merged on-line with 18-molybdodiphosphate heteropoly complex reagent to form a specific blue derivative that is subsequently detected spectrophotometrically at 820nm. The procedure has been optimized mainly with respect to measurement sensitivity. It is based on the leveling off of the refraction indices of the liquids mixed in the flow system by the careful matching of the refractive index of the reagent solution with that of the carrier and sample solutions. Amount as low as 0.5μmolL−1 of PAP, which corresponds to the 0.001% of PAP in paracetamol tablets, can be reliably determined using the proposed method, which is clearly below the specification limits recommended for PAP determination in paracetamol drug and tablet formulations (50ppm or 0.005% (w/w)). The developed method was successfully applied to the analysis of paracetamol formulations spiked with PAP and determination of PAP content in Rapidol tablets past their expiration date both by proposed SIA and reference HPLC methods.