ANALYTICAL METHOD VALIDATION AND IMPURITY PROFILING OF TIRZEPATIDE: A CRITICAL REVIEW FROM A REGULATORY QUALITY ASSURANCE PERSPECTIVE

Background: Tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, represents a significant advancement in the management of type 2 diabetes and obesity. However, its complex peptide structure necessitates robust analytical strategies to ensure quality, safety, and efficacy. Objective: The review aims to critically evaluate analytical method validation and impurity profiling approaches for tirzepatide from a regulatory quality assurance (QA) perspective. Methods: A comprehensive assessment of reported analytical techniques, including RP-HPLC, LC-MS/MS, and SEC-HPLC, is presented, with emphasis on their applicability in method validation and impurity characterisation. Results and Discussion: Key validation parameters such as accuracy, precision, linearity, and sensitivity are discussed in alignment with ICH Q2 guidelines. The role of stability-indicating methods and forced degradation studies in identifying critical degradants, including deamidation and oxidation products, is highlighted. Additionally, the importance of data integrity (ALCOA+) and risk-based approaches in ensuring regulatory compliance is emphasized. Conclusion: Robust analytical methodologies, supported by regulatory compliance and lifecycle management, are essential for maintaining the quality of tirzepatide. This review provides a concise framework to address analytical challenges associated with peptide therapeutics and supports the development of reliable QA strategies.