Comprehensive analysis of resveratrol metabolites in rats using ultra high performance liquid chromatography coupled with high resolution mass spectrometry

Resveratrol is an antitoxin secreted by plants such as Polygonum cuspidatum Sieb. et Zucc and Vitis vinifera L. when they are attacked by pathogens. In the present study, three methods were used to prepare biological samples, and then an efficient strategy based on ultra-high-performance liquid chromatography-linear ion trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap MS) was developed to screen and identify resveratrol metabolites in rat urine, plasma and faeces. As a result, a total of 56 resveratrol metabolites were screened and characterized. Among them, 39 metabolites were found in rat urine, while 6 and 16 metabolites were characterized from rat plasma and faeces, respectively. In addition, 56, 12 and 15 metabolic products were screened by solid phase extraction (method I), methanol precipitation (method II) and acetonitrile precipitation (method III), respectively, indicating that method I could be adopted as the most acceptable method. The results also demonstrated that resveratrol mainly underwent glucuronidation, glucosylation, sulfation, hydroxylation, dehydrogenation, hydrogenation, methylation and their composite reactions. Moreover, these metabolic reactions occurred to form a possible metabolic network that is similar to a triangular pyramid model. In summary, this research provides an idea for the further study of drug metabolism.