Integrated Application of Risk Management Techniques in Developing an Analysis Method for Traditional Chinese Medicine: A Case Study of a Percolation Solution for Xiaochaihu Capsules

Abstract

Risk management should run through the entire process of method development, utilization, and maintenance. Based on the analytical quality by design (AQbD) concept, various integrated risk management techniques were used in this study to develop an analysis method for the percolation solution of Xiaochaihu capsules. During the development of the analysis method, risk assessment was conducted using an Ishikawa diagram and failure mode effects analysis, followed by method optimization using experimental design. The probability of nonconformance calculated via an exhaustive Monte Carlo method quantitatively characterized the risk magnitude of method parameter failures, leading to the establishment of a operable design region method based on risk magnitude. Validation experiments and robustness tests of the data were utilized for model refinement and initial risk review. Methodological validation of the developed method was performed, and control strategies for the analysis method were presented through a decision tree. Stability experiments demonstrated that the samples remained stable at 4 °C for 24 h. The average recovery rate fell between 98.8% and 105%, with relative standard deviations ranging from 2.73% to 4.48%. The results showed that the established analysis method exhibited robustness. This analysis method can simultaneously determine the contents of uridine, adenine, 5-hydroxymethylfurfural, and guanosine. This method can also be employed for process control during percolation. This study integrated various risk management techniques to develop and maintain the analysis method, and this approach can potentially be extended to other analytical methods.