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

Paracetamol (PAR) and methocarbamol (MET) are co-formulated together in Methorelax (R) 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 mg mL(-1) for PAR, MET, 4-AP and GU, respectively. The method has been successfully applied in the analysis of Methorelax (R) 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.