Abstract

QUALITY BY DESIGN (QBD)-BASED UPLC ANALYTICAL METHOD DEVELOPMENT AND VALIDATION FOR THE ESTIMATION OF ANTICANCER DRUGS IN INJECTABLE DOSAGE FORMS: A COMPREHENSIVE REVIEW

Sabbavarapu Santhi Bhushan*, Rajiv Kukkar

ABSTRACT

Anticancer drugs administered through injectable dosage forms require stringent quality control because of their therapeutic potency, narrow therapeutic indices, complex physicochemical characteristics, and susceptibility to degradation. Reliable analytical procedures are therefore essential for the identification, assay, purity assessment, stability evaluation, and quality control of these pharmaceutical products. Ultra-performance liquid chromatography (UPLC) provides rapid, efficient, and sensitive chromatographic analysis and has become an important analytical platform for pharmaceutical quality assessment. However, conventional trial-and-error approaches to analytical method development may not adequately establish the relationship between analytical variables and method performance. Analytical Quality by Design (AQbD), derived from the Quality by Design (QbD)concept, provides a systematic, science- and risk-based strategy for analytical procedure development. This review discusses the application of QbD principles to UPLC method development and validation for anticancer drugs in injectable dosage forms. The review covers the Analytical Target Profile (ATP), critical method parameters, critical analytical responses, risk assessment, Design of Experiments (DoE), Central Composite Design (CCD), response surface methodology, method optimization, robustness, stability-indicating studies, and analytical method validation. Particular emphasis is placed on the application of AQbD for developing rapid and robust reversed-phase UPLC methods for anticancer injectable formulations. The integration of QbD with UPLC can reduce experimental variability, identify interactions among critical analytical variables, improve method robustness, and provide a scientifically justified analytical control strategy. The approach is consistent with the modern ICH Q14 and Q2(R2) framework and provides a suitable foundation for analytical lifecycle management.

Keywords: Anticancer drugs, injectable dosage forms, Quality by Design, Analytical Quality by Design, AQbD, UPLC, RP-UPLC, Design of Experiments, Central Composite Design, method validation, stability-indicating method.