Analysis of Major Impurities in Tolterodine Tartrate Tablets by 2D‐UPLC‐Q‐TOF/MS

RATIONALE: Impurity profiling is critical for the quality control and safety assessment of pharmaceutical formulations. Tolterodine tartrate tablets contain unknown impurities that are not documented in standard literature or pharmacopoeias. Identifying these impurities and determining their origin is essential for optimizing the manufacturing process and ensuring product stability. METHODS: at 350°C; scan range: m/z 50-1000). Impurity structures were elucidated by comparing their fragmentation patterns with tolterodine and considering the synthesis pathway. A comparative stability study of the API and tablets under stress conditions was conducted to trace impurity origins. RESULTS: Three primary impurities were detected and characterized in tablets from three different manufacturers, including the originator product. One previously unreported impurity (Impurity 1) was identified. Stability studies indicated that this impurity is a degradation product generated specifically during the tablet formulation process, not from the drug substance itself. CONCLUSIONS: The established 2D-LC/MS method is effective for the structural elucidation and source tracking of impurities in tolterodine tartrate tablets. The identification of a process-related degradation product provides direct insights for enhancing formulation strategies and implementing targeted quality control measures.