Integrating Second-Order Calibration with Analytical Quality by Design (AQbD) for Universal Calibration in Pharmaceutical Analysis

The quantitative determination of active pharmaceutical ingredients in complex matrices, such as pharmaceutical tablets from different manufacturers, poses challenges due to potential interference from various molecules, some of which may be unknown [1]. To address this issue, we have developed a novel and powerful approach by integrating second-order calibration with the Analytical Quality by Design (AQbD) framework for pharmaceutical analysis. Our focus was on drug analysis using second-order data with the AQbD approach, where we leveraged second-order calibration methods such as Rank Annihilation Factor Analysis (RAFA) and Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) using pH-wavelength data. The goal was to create a universal calibration model for the quantitation of acetylsalicylic acid (ASA, Aspirin) in different commercial formulations. By applying the AQbD approach and second-order calibration strategies, we successfully developed a calibration model with secondorder advantages. Second-order data, obtained from spectrophotometric monitoring of complex mixtures of several drug formulations at different pH levels, provided unique insights and enhanced the selectivity, sensitivity, and robustness of the analytical method in the presence of complex interfering matrices. This research highlights the effectiveness and novelty of integrating second-order calibration within the AQbD framework for pharmaceutical analysis. Our results demonstrate that secondorder calibration methods are powerful tools for developing universal calibration models, paving the way for more efficient and reliable [2] drug analysis in the pharmaceutical industry.