ACE under Stress: A Comprehensive Reviewof Stability Indicating Chromatographic Methods

Angiotensin-converting enzyme (ACE) inhibitors are still the cornerstone in the treatment of cardiovascular diseases and hypertension, but their wide range of chemical structures such as sulfhydryl, carboxylate, phosphate, and ester prodrugs make them susceptible to stress degradation. Stability- indicating chromatographic methods (SIMs) are thus critical for separating intact drug molecules from their hydrolytic, oxidative, hydrolytic, oxidative, photolytic, and thermal degradation products. This review gives an extensive account of published SIMs for ACE inhibitors that include high- performance liquid chromatography (HPLC), ultra- high- performance liquid chromatography (UHPLC), highperformance thin- layer chromatography (HPTLC), and hyphenated LC- MS methods. Described studies are critically discussed in relation to forced degradation approaches, chromatographic selectivity, validation parameters, and regulatory compliance with ICH Q1 A(R2), Q2(R2), and Q14 guidelines. Comparative discussion focuses on prevalent routes of degradation like ester hydrolysis to active acids, diketopiperazine formation and oxidative dimerization of sulfhydryl groups. Trends involve increased utilization of design- ofexperiments (DOE), peak- purity determination by PDA or MS, and the use of greener mobile phases. By distilling methodological progress and pitfalls, this review hopes to provide a handy guide for analysts designing sound, regulatory compliant stability- indicating assays for ACE inhibitors in bulk and pharmaceutical preparations