Simultaneous Determination of Paracetamol and Its Main Degradation Product in Generic Paracetamol Tablets Using Reverse-Phase HPLC

Abstract

A simple isocratic reversed-phase HPLC method was developed and validated for the determination of paracetamol and p-aminophenol, its major degradation impurity, in the pharmaceutical tablets. The analytes were separated on a C18 Inertsil® ODS-3 column (250 mm x 4.60 mm i.d., 5 μm particle size). A mobile phase, MeOH: 0.01M phosphate buffer pH 5.0 (30:70 v/v) at flow rate of 1 ml/min was suitable for the separation and determination of paracetamol and p-aminophenol. The UV detection was carried out at 243 nm. The chromatographic parameters such as retention times, capacity factor, tailing factor, number of theoretical plates, %RSD of peak area and resolution factors were determined. The developed method was found to be linear over concentration ranges of 2.5 - 20 μg/ml (r2 = 0.9992 and 0.9997 for paracetamol and p-aminophenol, respectively). The limit of detection (LOD) for paracetamol and p-aminophenol were 0.06 and 0.5 μg/ml, respectively. The limit of quantification (LOQ) for paracetamol and p-aminophenol were 0.75 and 1.0 μg/ml, respectively. Validation acceptance criteria were met in all cases. The developed method was successfully applied to determine paracetamol and p-aminophenol in five generic paracetamol tablets in Thailand.