(527d) Root Cause Analysis of Quality Defects Using Knowledgebase of HPLC-MS Fingerprint for Quality Control of Botanical Drug Product

The quality control of botanical drug product or traditional Chinese medicines (TCMs) has always been an important issue for achieving consistent efficacy and is increasingly attracted more and more attention all over the world. In this work, a methodology for batch-to-batch quality control using based on HPLC-MS fingerprints and process knowledgebase was proposed, taking the manufacturing process of Panax notoginseng preparation as a case study. HPLC-MS fingerprint analysis method was established and the fingerprints of the preparation produced under normal and abnormal operation conditions were collected. Based on multivariate statistical analysis, process knowledge was obtainted and the cause effect relationship between process deviations and quality defects was revealed. Multivariate statistical models were built for fault detection and discriminate analysis models were built using Hotelling T2 and DModX for fault diagnosis. The results have shown that the quality defects were detected successfully by multivariate statistical control charts and the type of process deviations were diagnosed correctly by discriminate analysis. This work has demonstrated the applicability of combining HPLC-MS fingerprints, process knowledge and multivariate analysis for the quality control of botanical drug product.