Abstract

ANALYTICAL QUALITY BY DESIGN (AQBD)-DRIVEN RP-HPLC METHOD DEVELOPMENT FOR TARGETED ANTICANCER AGENTS: REGULATORY ADVANCES, CHROMATOGRAPHIC STRATEGIES, AND FUTURE PERSPECTIVES)-DRIVEN RP-HPLC METHOD DEVELOPMENT FOR TARGETED ANTICANCER AGENTS: REGULATORY AD

*Dipali Diwate

Abstract

The increasing complexity of modern pharmaceutical products has intensified the need for robust, reliable, and scientifically justified analytical methodologies. Reverse-phase highperformance liquid chromatography (RP-HPLC) remains the most widely utilized analytical technique in pharmaceutical research and quality control because of its versatility, sensitivity, and reproducibility. Traditionally, chromatographic method development relied heavily on empirical experimentation and sequential optimization approaches, often resulting in methods with limited robustness and inadequate understanding of critical variables. The introduction of Analytical Quality by Design (AQbD) has transformed analytical method development by incorporating systematic risk assessment, statistical experimental design, lifecycle management, and regulatory science principles. AQbD facilitates a deeper understanding of analytical procedures through the identification of Analytical Target Profiles (ATPs), Critical Quality Attributes (CQAs), and Critical Method Parameters (CMPs), ultimately leading to the establishment of Method Operable Design Regions (MODRs). In parallel, recent regulatory developments, including ICH Q14 and ICH Q2(R2), have reinforced the importance of science-based analytical development and continuous performance verification. Targeted anticancer therapies such as osimertinib present unique analytical challenges due to their complex physicochemical characteristics, stringent impurity requirements, and increasing regulatory scrutiny. This review critically examines the evolution of AQbD, modern RP-HPLC method development strategies, regulatory expectations, and recent advances in chromatographic science. Particular emphasis is placed on targeted oncology products and osimertinib as a representative case study. Emerging technologies including artificial intelligence, digital chromatography, and green analytical chemistry are also discussed as future directions for pharmaceutical analytical science.

Keywords: Analytical Quality by Design; AQbD; RP-HPLC; Osimertinib; Targeted Anticancer Therapy; ICH Q14; Method Development; Pharmaceutical Analysis.