RP-HPLC Method Development and Validation for Quality Control and Forced Degradation Analysis of Paracetamol–Ibuprofen Multi-Component Formulations

Abstract

This study presents the development and validation of a robust reverse-phase high-performance liquid chromatography method for the simultaneous estimation of paracetamol and ibuprofen in multi-component pharmaceutical formulations. Paracetamol and ibuprofen are widely prescribed analgesic and antipyretic agents, frequently co-formulated to enhance therapeutic efficacy. Analytical challenges arise due to overlapping absorbance spectra, distinct physicochemical properties, and susceptibility to degradation under stress conditions. To address these challenges, an isocratic reverse-phase high-performance liquid chromatography method was optimized using a mobile phase of acetonitrile and phosphate buffer (pH 3.0) in a 60:40 v/v ratio, with detection carried out on a PDA detector at 220–230 nm. Method validation was performed in accordance with ICH Q2(R1) guidelines, evaluating parameters such as linearity, accuracy, precision, specificity, robustness, and sensitivity. The method demonstrated excellent resolution, with paracetamol and ibuprofen eluting at approximately 2.5 and 5.2 minutes, respectively. Forced degradation studies confirmed the stability-indicating capacity, with paracetamol showing higher degradation under acidic conditions and ibuprofen under oxidative stress. Linearity was established in the range of 10–100 µg/mL for both drugs, with correlation coefficients exceeding 0.999. The limits of detection and quantitation were sufficiently low, confirming suitability for trace analysis. Robustness testing indicated consistent performance under minor variations in flow rate, pH, and detection wavelength. Overall, the method proved to be accurate, precise, and stability-indicating, making it suitable for routine quality control, regulatory submissions, and stability testing of fixed-dose paracetamol–ibuprofen formulations. This validated reverse-phase high-performance liquid chromatography technique offers a reliable analytical framework that can be extended to other multi-component pharmaceutical preparations.