Analytical quality by design based on knowledge organization: A case study of developing an ultrahigh-performance liquid chromatography method for the detection of phenolic compounds

IntroductionDespite numerous successful cases, there are still some challenges in using analytical quality by design (AQbD) for the development of analytical methods. Knowledge organization helps to enhance the objectivity of risk assessment, reduce the number of preliminary exploratory experiments, identify potential critical method parameters (CMPs) and their scope.ObjectiveIn the present study, we aimed to develop a simple, rapid, and robust analytical method for detecting phenolic compounds in Xiaochaihu capsule intermediates utilizing knowledge organization.MethodsKnowledge organization and AQbD were combined to obtain the initial analytical conditions through knowledge collection, extraction, reorganization, and analysis. The quantitative relationship between critical method attributes (CMAs) and CMPs was then established by a definitive screening design. The method operable design region was calculated using an exhaustive Monte Carlo approach based on the probability of reaching the standard. Robustness investigation and methodological validation were finally performed.ResultsAnalytical target profiles, CMAs, potential CMPs, and initial analytical conditions were initially identified, and the optimized ranges of operating parameters were obtained. A UHPLC method was successfully established for the analysis of phenolic compounds in ginger-ginger pinellia percolate, and the method validation outcomes were also satisfactory.ConclusionThe developed method can be a reliable means to detect the phenolic compounds of Xiaochaihu capsule intermediates. Knowledge organization provides a new approach for making better use of prior knowledge, significantly enhancing the efficiency of analytical method development. The approach is versatile and can be similarly applied to the development of other methods. This study employed an AQbD process based on knowledge organization to develop an analytical method for detecting phenolic compounds in Xiaochaihu capsule intermediate, improving the efficiency of conducting single-factor experiments and identifying potential CMPs in the early stage of method development. Simultaneously, it offers a new approach for utilizing prior knowledge effectively. This analytical method can be used for quality control of intermediate in Xiaochaihu capsule.