Q-marker based strategy for CMC research of Chinese medicine: A case study of Panax Notoginseng saponins.

Background: To ensure pharmaceutical quality, chemistry, manufacturing and control (CMC) research is essential. However, due to the inherent complexity of Chinese medicine (CM), CMC study of CM remains a great challenge for academia, industry, and regulatory agencies. Recently, quality-marker (Q-marker) was proposed to establish quality standards or quality analysis approaches of Chinese medicine, which sheds a light on Chinese medicine's CMC study.

Purpose: Here manufacture processes of Panax Notoginseng Saponins (PNS) is taken as a case study and the present work is to establish a Q-marker based research strategy for CMC of Chinese medicine.

Study Design: The Q-markers of Panax Notoginseng Saponins (PNS) is selected and established by integrating chemical profile with pharmacological activities. Then, the key processes of PNS manufacturing are identified by material flow analysis. Furthermore, modeling algorithms are employed to explore the relationship between Q-markers and critical process parameters (CPPs) of the key processes. At last, CPPs of the key processes are optimized in order to improving the process efficiency.

Results: Among the 97 identified compounds, Notoginsenoside R, ginsenoside Rg, Re, Rb and Rd are selected as the Q-markers of PNS. Our analysis on PNS manufacturing show the extraction process and column chromatography process are the key processes. With the CPPs of each process as the inputs and Q-markers' contents as the outputs, two process prediction models are built separately for the extraction process and column chromatography process of Panax notoginseng, which both possess good prediction ability. Based on the efficiency models of extraction process and column chromatography process we constructed, the optimal CPPs of both processes are calculated.

Conclusion: Our results show that the Q-markers derived from CMC research strategy can be applied to analyze the manufacturing processes of Chinese medicine to assure product's quality and promote key processes' efficiency simultaneously.