A Stability-Indicating HPLC-PDA Method for Simultaneous Determination of Paracetamol, Caffeine, Ibuprofen and their Degradation Products in Solid Dosage Forms

Purpose of this study was to develop a stability-indicating RP-HPLC method for routine analysis of Paracetamol (PARA), Caffeine (CAF) and Ibuprofen (IBU) in their combined solid dosage forms. The new RP-HPLC method was validated as per ICH, FDA and USP guidelines with respect to accuracy, precision, specificity, linearity, solution stability, robustness, sensitivity and system suitability. The method was developed by using a binary gradient mode of phosphate buffer (pH 7.2) and acetonitrile at a flow rate of 1.3mL/min for 15 minutes over C-18 (ODS, 150 x 4.6 mm, 5µm) column at ambient temperature. Injection volume was 20µL for both standard and sample solutions and the eluents were monitored with UV detection at 230nm.Accuracy was determined by the recovery tests of the drugs and found to be within a range of 99.89% to 100.33%. Intraday and inter-day precisions were demonstrated by a relative standard deviation being far less than maximum allowable limit (2.0%, according to FDA). The method showed linear response with a correlation coefficient (r2) value of 0.999 for all three drugs. Forced degradation studies in acidic, basic, oxidation and reduction media were carried out to establish the stability indicating tolerance of this method. Specificity was shown by the separation of drugs with high degree of resolution between them and absence of any interference from the excipients or degradation products. This method was successfully applied to assay the drugs in tablets and capsules. Hence this newly developed method can be considered suitable and reliable for the routine analysis of PARA, CAF and IBU in their solid dosage forms.