Metabolites and Metabolic Pathway Analysis of Germacrone in Rats by UHPLC-Q-Orbitrap HRMS

OBJECTIVE To study the metabolites of germacrone in rats and explore its possible metabolic pathway. METHODS The biological samples of rats(plasma, urine and feces) were analyzed after intragastric administration germacrone(10 mg·kg^-1) by UHPLC-Q-Orbitrap HRMS. The chromatographic Waters ACQUITY UPLC^® BEH C₁₈(2.1 mm×50 mm, 1.7 μm) column was used and the mobile phase was acetonitrile-0.1% formic acid aqueous solution with gradient elution. The Q-Exactive high-resolution mass spectrometer equipped HESI ion source was adopted. Auxiliary temperature and ion transport tube temperature were set at 300℃ and 320℃. Spray voltage was +3.50 kV or -2.80 kV and scanning mode was Full MS/dd-MS². The quasi-molecular ion peaks and fragment ion information provided by high resolution mass spectrometry in administration group and blank group were analyzed and compared. Xcalibur 3.0, Mass Frontier 2.0 and Compound Discovery 2.1 software were used for data processing to screen and identify potential metabolites. RESULTS Twenty three protocompound and metabolites were screened and identified in the biological samples of rats, and the main metabolic reactions of germacrone in rats were dehydration reaction, desaturation reaction, oxidation reaction, glucosamine binding reaction, glucosaldehyde acidification reaction and related complex reaction, etc. CONCLUSION In this study, the metabolic process of germacrone in rats is elucidated in detail, and its metabolic pathway is analyzed, which can provide theoretical basis for the further study of pharmacodynamics, pharmacokinetics and toxicology of germacrone.