Validated stability indicating RP-HPLC method for determination of paracetamol, methocarbamol and their related substances

Abstract

Paracetamol (PAR) and methocarbamol (MET) are co-formulated together in Methorelax® tablets which are widely used as a muscle relaxant and in the treatment of muscle-skeletal pain. On the other hand, 4-aminophenol (4-AP) and guaifenesine (GU) have been reported to be related substances and degradation products of PAR and MET, respectively. The target of this work was to develop and validate a simple, sensitive and selective stability indicating RP-HPLC method for the determination of PAR, MET, 4-AP and GU in their bulk powders and laboratory prepared mixtures. Chromatographic separation was achieved within 10 minutes with the required asymmetry, accuracy and precision on ODS column using 0.05 M KH₂PO₄ buffer : acetonitrile (72.5 : 27.5, v/v, pH = 6) as the mobile phase at a flow rate of 1 mL min⁻¹ with UV detection at 225 nm. The developed method has been validated as per ICH guidelines and the calibration plots were linear over the concentration ranges of 3–20, 4–25, 0.6–8 and 0.6–8 μg mL⁻¹ for PAR, MET, 4-AP and GU, respectively. The method has been successfully applied in the analysis of Methorelax® tablets and good results were obtained. Moreover, its results have been compared to a previously reported RP-HPLC method and no significant difference was found between the two methods.