DEVELOPMENT AND VALIDATION OF STABILITY-INDICATING RP-UPLC METHODS FOR DETERMINATION OF DRUGS IN PHARMACEUTICAL DOSAGE FORMS: A COMPREHENSIVE REVIEW

Abstract

Stability-indicating analytical methods are essential for assessing the quality, safety, and stability of pharmaceutical products throughout their lifecycle. Reverse-phase ultra-performance liquid chromatography (RP-UPLC) has emerged as an efficient analytical technique because of its high chromatographic efficiency, rapid separation, improved resolution, and reduced solvent consumption. The development of a stability-indicating method requires appropriate forced degradation studies, effective separation of the drug from degradation products, and comprehensive validation. In recent years, Analytical Quality by Design (AQbD) has transformed analytical method development from empirical trial-and-error experimentation toward a systematic, science- and risk-based approach. AQbD incorporates the Analytical Target Profile (ATP), risk assessment, Critical Method Parameters (CMPs), Design of Experiments (DoE), statistical modelling, and establishment of a Method Operable Design Region (MODR) (Xuan et al., 2024). This review discusses the principles and applications of stability-indicating RP-UPLC methods, forced degradation studies, chromatographic optimization, AQbD implementation, statistical experimental design, analytical validation, and regulatory expectations under ICH Q2(R2) and Q14.