Impurity Profiling of Antidiabetic Drugs: Analytical Challenges and Regulatory Perspectives

Abstract

Impurity profiling has emerged as a critical component of pharmaceutical quality assurance, particularly for antidiabetic drugs that are intended for long-term and often lifelong therapy. The presence of impurities—originating from raw materials, manufacturing processes, degradation pathways, or drug–excipient interactions—can significantly impact the safety, efficacy, and stability of antidiabetic formulations. With the increasing complexity of modern antidiabetic agents, including biguanides, sulfonylureas, thiazolidinediones, DPP-4 inhibitors, SGLT-2 inhibitors, and combination therapies, comprehensive impurity profiling has become both analytically challenging and regulatory-driven. This review provides an in-depth discussion on the sources and classification of impurities in antidiabetic drugs, analytical strategies employed for their identification, quantification, and characterization, and the evolving regulatory expectations governing impurity control. Emphasis is placed on stability-indicating methods, forced degradation studies, and hyphenated analytical techniques such as LC–MS/MS and NMR for structural elucidation. Current challenges, including trace-level impurity detection, genotoxic impurity assessment, and impurity profiling in fixed-dose combinations, are critically evaluated. The review aims to offer a comprehensive perspective to researchers and industry professionals engaged in the development, validation, and regulatory submission of antidiabetic drug products.