Pharmaceutical process-omics for quality control of traditional Chinese medicine preparations: A 1H-qNMR assisted case study of Guanxinning injection

Abstract

Guanxinning injection (GXNI) is a traditional Chinese medicine preparation derived from Salviae Miltiorrhizae Radix et Rhizoma and Chuanxiong Rhizoma. It is produced through a series of processes involving water extraction, ethanol precipitation, and other techniques. GXNI is primarily used for treating angina pectoris in coronary heart disease, and it has shown remarkable efficacy in clinical practice. One of the key components responsible for its pharmacological effects is salvianolic acids. However, these components are known for their poor stability and susceptibility to pH and temperature variations. Therefore, it is crucial to focus on ensuring the quality and stability of salvianolic acids in GXNI. In this study, we employed Proton nuclear magnetic resonance (1H NMR) to analyze the intermediate products formed during the manufacturing of GXNI. We thoroughly examined the spectra of these intermediates and developed a precise 1H-qNMR method for the accurate quantification of various classes of chemical components present in GXNI. Additionally, we applied this method to investigate how the composition of GXNI evolves and transfers throughout the entire production process. To further enhance our understanding, we employed Principal Component Analysis (PCA) and Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) to identify critical steps in the production process and to identify potential quality markers (Q-markers) associated with these processes. Our study sheds light on the dynamic changes in composition that occur during the production of GXNI. This research serves as a foundation for establishing a comprehensive quality evaluation system for GXNI, ensuring its efficacy and safety in clinical applications.