Abstract

HPLC FOR IMPURITY PROFILING AND QUANTIFICATION IN PHARMACEUTICALS: REGULATORY DEMANDS AND ADVANCED ANALYTICAL STRATEGIES

Lina G. Shimpi, Roshni D. Patil*, Yash S. Gaikwad, Shailesh S. Chalikwar

ABSTRACT

High-performance liquid chromatography (HPLC), which makes precise impurity detection, profiling, and quantification possible, is a crucial component in guaranteeing the quality of pharmaceutical products. These pollutants, which range from genotoxic chemicals to degradation products and process-related contaminants, represent serious safety risks and are therefore closely regulated. This thorough analysis critically assesses the changing field of pharmaceutical impurity control, exploring the classification of impurities, the specific regulatory requirements under important ICH guidelines (Q3A, Q3B, M7, Q3C, and Q3D), and the significant influence of nitrosamine contamination on new analytical paradigms. We discuss robust lifecycle control strategies combined with Quality by Design (QbD) principles, modern and sophisticated approaches for trace-level detection, the critical role ofhyphenated techniques like LC-MS/MS and LC-QTOF-MS in the identification of unknowns, and state-of-the-art sample preparation technologies. The goal of this article is to give researchers and quality control experts who are working toward strong impurity management with HPLC a critical and forward-looking guide. It also lays the groundwork for future developments such as Ultra-High Performance Liquid Chromatography (UHPLC), sophisticated automation, and the incorporation of AI-driven analysis.

Keywords: Impurity profiling, HPLC, UHPLC, ICH guidelines, Genotoxic impurities, Nitrosamines, Hyphenated techniques, LC-MS/MS, QbD. Trace analysis, Regulatory compliance, Automation, Data integrity.