Published Paper Details:

Pharmaceutical products are vulnerable to degradation during manufacturing, storage, and distribution, which can adversely affect their safety, efficacy, and quality. Forced degradation (stress testing) is a systematic approach used during drug development to deliberately degrade active pharmaceutical ingredients (APIs) and drug products under exaggerated conditions such as hydrolytic, oxidative, photolytic, thermal, and humidity stress. Data generated from these studies support the development of stability-indicating analytical methods (SIAMs) that can selectively quantify the intact drug in the presence of its degradation products and impurities. Impurity profiling, which involves the detection, identification, characterization, and quantification of process- and degradation-related impurities, is essential to comply with International Council for Harmonisation (ICH) impurity guidelines and to ensure patient safety. This review summarizes the scientific principles of forced degradation, typical stress conditions, degradation mechanisms, and their relevance in understanding the intrinsic stability of drug substances. It further discusses the development and validation of stability-indicating methods, with emphasis on high-performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS), nuclear magnetic resonance (NMR), Fourier transform infrared (FTIR) spectroscopy, and other hyphenated techniquesforimpurity profiling.Regulatory expectations from ICH Q1A(R2), Q1B, Q2(R1), Q3A(R2), and Q3B(R2), as well as USFDA and pharmacopeial recommendations, are highlighted. Concepts of mass balance and case studies on stability- indicating method development are also presented. Emerging trends such as high-resolution mass spectrometry, two-dimensional chromatography, chemometrics, and risk-based impurity assessment are briefly reviewed. Forced degradation and robust stability-indicating methods together form the backbone of impurity profiling strategies that ensure safe, effective, and stable pharmaceutical products throughout their shelf life.