Analytical method development for new compound Chinese patent medicines based on the AQbD concept: A case study of Qiwei Fangjihuangqi Granule

Based on the analytical quality by design (AQbD) concept, a quantitative fingerprint method was developed simultaneously for two types of materials used in the pharmaceutical manufacturing process of Qiwei Fangjihuangqi Granule (QFG), namely the intermediate and the preparation. A structured literature analysis strategy was applied for prior knowledge management, in which 351 publications involving 366 analytical methods were systematically analyzed to establish optimized initial conditions. A definitive screening design (DSD) was subsequently employed to identify six critical method parameters (CMPs), and stepwise regression was used to establish quantitative models between critical quality attributes (CQAs) and CMPs, all exhibiting R2 values greater than 0.90. A method operable design region (MODR) was then constructed based on acceptable risk thresholds combined with Monte Carlo simulations and successfully validated. Under the optimized analytical conditions, thirteen components derived from six medicinal materials were quantitatively determined, and the established method was successfully applied to ten batches of QFG, yielding fingerprint similarity values ranging from 0.988 to 1.000. The proposed prior-knowledge management strategy provides a feasible approach for AQbD-based analytical method development in the research and development of new Chinese medicines.