Characterization of lignans in Forsythiae Fructus and their metabolites in rats by ultra-performance liquid chromatography coupled time-of-flight mass spectrometry

Objectives This study was designed to profile the chemical information of Forsythiae Fructus (FF) and investigate thein-vivoFF-related xenobiotics, especially for lignans. Methods Rats were oral administrated of FF and pinoresinol-4-O-glucoside, respectively. Blood and urine samples were collected after ingestion, and xenobiotics was profiled by an UPLC/Qtof MS method. Key findings A total of 19 lignans were identified or tentatively characterized in FF, and 63 lignan-related xenobiotics were found in rat plasma and urine after ingestion of FF. It was found that lignans could be transformed into metabolites by furan ring opening, hydrogenation, demethylation, dehydration and phase II reactions (sulfation and glucuronidation). The whole metabolic behaviour of bisepoxylignan was revealed by evaluating the metabolism of pinoresinol-4-O-glucosidein vivo. It was found that the configuration of C-8/C-8MODIFIER LETTER PRIME was retained after furan ring opening and metabolic reactions always occurred at position of C-3/C-4/C-5 or C-3MODIFIER LETTER PRIME/C-4MODIFIER LETTER PRIME/C-5MODIFIER LETTER PRIME. Additionally, other types components in FF andin vivowere also characterized. Conclusions This work revealed thein-vivometabolism of FF, and reported the characteristic metabolic reactions of lignans for the first time. It was also provided the foundation for the further investigation on pharmacodynamic components of FF or TCMs containing FF.