Determination of 4-aminophenol impurities in multicomponent analgesic preparations by HPLC with amperometric detection.

A method for the determination of 4-aminophenol, the main impurity of paracetamol, by high-performance liquid chromatographic (HPLC) method with amperometric detection has been developed. The analysis was performed in an isocratic mode on a reversed phase Luna column 5 microm C-18 (100 x 4.6 mm). A mobile phase (0.05 mol l(-1) LiCl solution containing 18% methanol adjusted to pH 4.0 with orthophosphoric acid) was suitable for the separation and determination of 4-APh. Chromatograms were recorded for 250 s by means of an amperometric detector at a potential of +325 mV of the glassy carbon electrode versus the reference electrode Ag/AgCl. The proposed liquid chromatographic method was successfully applied to the analysis of commercially available multicomponent dosage forms. The sensitivity of the detection for 4-aminophenol was 1 ng ml(-1) for substance and 4 ng ml(-1) for tablets or capsules. The method developed in this study is sensitive and selective and can be applied for routine studies of pharmaceuticals in the form of tablets or capsules.

Determination of 4-aminophenol impurities in selected pharmaceutical preparations by HPLC method with amperometric detection.

4-Aminophenol (4-APh) is the main impurity present in preparations containing paracetamol. Using the cyclic voltammetry and differential pulse voltammetry methods, the electrode behaviour of 4-APh has been studied in various non-buffered and buffered solutions at glassy carbon and golden electrodes. By means of the high-performance liquid chromatography with amperometric detection (HPLC-EC), the dependency of current intensities of the 4-APh peaks on the potential in the range (0-600 mV in the pH range 2-5, the ionic strength of mobile phase ranging from 0.01 mol (-1) to 0.20 mol l(-1) LiCl, has been studied. While employing the HPLC-EC method in this work, a glassy carbon electrode was used as the amperometric detector. The optimal potential selected in this research was +325 mV. It was found that a 0.05 mol l(-1) LiCl solution, containing 18% of methanol, at pH 4.0 adjusted with orthophosphoric acid, is suitable for the separation of 4-APh and paracetamol from each other and from other pharmaceutical excipients present in tablets. By using the elaborated HPLC-EC method, the content of 4-APh (at concentrations from 4 ng ml(-1)) in the paracetamol from Aldrich and in tablets from different producers, containing 500 mg of paracetamol in a tablet was found. Statistical evaluation of the obtained results has shown that the proposed HPLC-EC method for the determination of 4-APh is characterized by a good accuracy and precision (RSD about 6%) and can be applied to routine investigations of pharmaceutical preparations in the form of tablets.