Systematic Analysis of Chemical Constituents and Pharmacokinetics of Baihe Dihuang Decoction In Vivo by UHPLC-MS/MS

Baihe Dihuang decoction (BDD), composed of Lilii Bulbus and Rehmanniae Radix, is a classical Chinese herbal formula. It demonstrates clinical applications in treating emotional disorders and anxiety. In this study, we characterized the chemical basis of BDD in vitro and elucidated its metabolic pathways, pharmacokinetic profiles, and tissue distribution in vivo. An ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) was used to qualitatively characterize the chemical constituents and their metabolites in rat plasma after oral administration of BDD. Then a reliable, sensitive, and accurate quantitative method based on an ultra-high performance liquid chromatography triple quadrupole mass spectrometry (UHPLC-QqQ-MS) was employed to investigate the pharmacokinetics of nine major compounds and the tissue distribution of six of these compounds in rats. Results showed that 97 constituents including iridoid glycosides, phenylethanoid glycosides, phenolic acid glycerides, alkaloids, and other types of components were identified in BDD. A total of 28 prototype constituents and 66 metabolites were identified in rat plasma samples. The related metabolic pathways mainly involved deglycosylation, methylation, and deoxygenation. The pharmacokinetic results showed that the analytes displayed rapid absorption and elimination. Tissue distribution analysis revealed that all analytes were detected in heart, liver, spleen, lung, and kidney at 0.5 h after administration and presented higher concentrations in the lung and kidney compared to other tissues. This study provides a reference for clinical application and new drug development of BDD.