Reconstruction of quality marker system for Ginkgo Folium tablet using UHPLC‐Q‐Orbitrap MS, quantum chemical calculation, network pharmacology, and molecular simulation

Abstract Introduction Ginkgo Folium tablet (GFT) is a patented traditional Chinese medicine prepared from Ginkgo biloba leaves extract (GBE). However, the current quality indicators for GFT or GBE as designated by the Chinese Pharmacopoeia are insufficient in preventing counterfeit events. Objective This study aimed to putatively identify compounds in GFT and to further develop a quality marker (Q‐marker) system for GFT. Methods A novel strategy utilizing database‐aided ultrahigh‐performance liquid chromatography‐quadrupole‐orbitrap mass spectrometry was employed to analyze the lyophilized aqueous powder of GFT. Subsequently, the identified compounds underwent quantum chemical calculations, network pharmacology, and molecular simulations through in silico approaches to evaluate the Q‐marker principles of traceability, specificity, and efficiency‐relevance. Results The results revealed the putative identification of a total of 66 compounds, including 36 flavonoids, 7 phenolic acids and derivatives, 5 terpene lactones, 4 fatty acids and derivatives, 3 alkaloids, 1 amino acid, and 10 other compounds. Particularly, 16 compounds were unexpectedly observed, and seven compounds met the Q‐marker principles. Conclusion This study recommends the seven compounds, namely, (−)‐gallocatechin, matrine, (−)‐epicatechin, ginkgolide C, ginkgolide A, ginkgolide B, and curdione, as the anti‐counterfeiting pharmacopoeia Q‐markers for GFT. The reconstruction of the Q‐marker system for GFT not only enhances the understanding of the compounds in GFT and other GBE‐based preparations but also provides valuable recommendations for the Pharmacopoeia Commission.