Development and Validation of a Stability-Indicating rp-hplc method for Simultaneous Estimation of Paracetamol, Aceclofenac, and their related Substances in Bulk and Pharmaceutical Dosage Forms

The accurate quantification of related substances (RS) in pharmaceutical formulations is a critical aspect of ensuring drug safety, efficacy, and regulatory compliance. This review presents a comprehensive summary of the development and validation of a reverse-phase high-performance liquid chromatography (RP-HPLC) method for the simultaneous estimation of Paracetamol and Aceclofenac along with their pharmacopoeial and process-related impurities. The method was systematically optimized through solubility screening, buffer pH adjustment, gradient elution programming, and column selection, utilizing a pH-stable C18 stationary phase coupled with ion-pairing agents to achieve optimal peak resolution. Method validation was conducted following ICH Q2 (R1) guidelines, evaluating parameters such as specificity, linearity, sensitivity, precision, accuracy, and robustness. The method demonstrated excellent linearity (R² > 0.999), low limits of detection and quantification for all analytes, and high recovery rates within acceptable ranges. Importantly, critical resolution between closely eluting impurities, such as Aceclofenac Impurity-A and 4-chloroacetanilide, was successfully achieved, confirming the method’s suitability for routine quality control. The study underscores the importance of robust analytical design in impurity profiling and offers a validated approach that can be adopted for regulatory submissions and real-time release testing in the pharmaceutical industry.