Identification of major bioactive components and their metabolites in rat plasma after oral administration of Zhikebao tablet by UHPLC-QTOF-MS / 药学学报

ABSTRACT

An ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) method was established to identify the metabolites in rat plasma after oral administration of Zhikebao tablets. The high-resolution mass spectrometer was operated in positive and negative ion mode, respectively. First, full-scan was applied, which was dependent on a multiple mass defect filter (MMDF) combined with dynamic background subtraction (DBS). These were utilized to trigger the information dependent acquisition (IDA) function in the experiment. For the IDA criteria, the eight most intense candidate ions of per cycle were selected to do a product ion scan. Then Metabolite Pilot 2.0 software was utilized to load data to seek possible metabolites. The analytical models employed by Metabolite pilot 2.0 were established for representative compounds of the Papaveris Pericarpium and licorice in Zhikebao tablet. Finally, metabolites were identified according to accurate mass measurement and retention time. 38 components from the rat plasma after oral administration of the drug have been found, including 5 prototype opium alkaloids, liquiritin, glycyrrhizic acid and 31 relative metabolites. The metabolic transformation of Zhikebao tablet in rats was mainly induced by glucuronidation, sulfation, methylation, amine to carboxylic acid, hydrolysis and so on. In this paper, the metabolites of the main active components of Zhikebao tablet were tentatively identified, and the metabolic pathway was compared with that of single chemical drugs. Moreover, it laid the fundamental elucidation of further metabolism study of Zhikebao tablet or other compound traditional Chinese medicine preparations which containing Papaveris Pericarpium or licorice.