Comprehensive metabolic profiling and quantitative analysis of key constituents in compound licorice tablets using UHPLC-Q-exactive orbitrap MS

Abstract

Herbal medicines (HMs) and their preparations typically exert therapeutic effects through the synergistic action of multiple bioactive components. In vivo metabolism studies and quality control through component quantification are essential for understanding the therapeutic material basis and ensuring safety. In this study, an UHPLC-Q-Exactive Orbitrap MS method was established to comprehensively analyze the chemical constituents of compound licorice tablets (CLQTs) and their metabolites in plasma, urine, and feces of male Sprague–Dawley rats after oral administration. A total of 59 components were identified or tentatively characterized in CLQTs, including 7 alkaloids, 36 flavonoids, 13 triterpenoid saponins, 1 coumarin, 1 phenolic acid, and 1 other compound, with 12 compounds confirmed by reference standards. Additionally, 99 xenobiotics, including 40 parent compounds and 59 metabolites, were detected, with 22 in plasma, 66 in urine, and 58 in feces. The in vivo metabolic profiles of flavonoids, alkaloids, and triterpenoid saponins were further elucidated. Moreover, a quantitative analysis of four key components from 156 batches of CLQTs was performed using a single-marker method for multi-component quantification. The results showed good consistency with the standard curve method, demonstrating reliable quality control of CLQTs. To the best of our knowledge, this is the first comprehensive study of the in vivo metabolic profiles of CLQTs, providing valuable insights into the identification of effective substances and their mechanisms of action. These findings lay a solid foundation for future pharmacological studies and the clinical application of CLQTs.