Chemical Composition Analysis Of Heshuxiaoji Pills And Its Metabolism In Primary Hepatocellular Carcinoma Model Mice

Objective:To identify the main chemical components of Heshuxiaoji pills and analyze its prototype components and metabolites in the blood,urine and feces of Hepatoma 22(H22)tumor-bearing mice,so as to lay the foundation for clarifying the material basis of Heshuxiaoji pills and further exploring its pharmacodynamics.Methods:Ultra high performance liquid chromatography-tandem high resolution mass spectrometry(UHPLC-HR-MS)was used to analyze the crude drug samples of Heshuxiaozhi pills.Combined with Xcalibur software,the total ion chromatogram was measured to obtain the molecular weight,retention time,secondary ion fragments,isotope abundance and other information.The main chemical constituents in Heshuxiaoji pills were identified by comparing the patterns of positive and negative ions,searching literature reports and chemical constituents database of traditional Chinese medicine.On this basis,the H22 hepatoma tumor-bearing mice model was constructed.Venous blood,urine and feces samples were collected before and after gavage and Shuxiaoji pills.The UHPLC-HR-MS technology was used again to identify the prototype chemical composition and metabolites of Heshuxiaoji pills in the blood,urine and feces of H22 hepatoma tumor-bearing mice.Results:1.A total of 150 compounds were identified from Heshuxiaoji pills,among which 37 compounds were confirmed by comparison with standard substances.Results A total of 150 compounds were identified from Heshuxiaoji pills,including 68 flavonoids,29 phenolic acids,15 terpenoids,14 alkaloids,6phenylglycolins,5 phenylpropyl compounds,4 carbohydrates and derivatives,3saponins and 2 steroid compounds.There were 2 lignan compounds,1 glycoside compound and 1 Kun compound.And the source of the medicinal materials of the above chemical components were attributed,and the chemical components of Heshuxiaoji Pills were systematically identified.2.43 chemical components,including 27 prototype components and 16 metabolites,were identified from the blood,urine and feces of the mice after gavage and Shuxiaoji pills.The prototype components included 18 flavonoids,3 phenytosides,5 terpenoids,and1 phenolic acid component.The first phase metabolites were mainly oxidative metabolites,and the second phase metabolites mainly included glucuronidation and methylation metabolites.Conclusion:1.Based on UHPLC-HR-MS technology,150 chemical components were successfully identified from Heshuxiaoji pills,mainly flavonoids,phenolic acids,terpenoids and alkaloids.2.43 components(27prototype components and 16 metabolites)were identified from the blood,urine and feces of H22 hepatoma tumor-bearing mice,and the absorption and metabolism of Heshuxiaoji pills in vivo were preliminly elucidated.3.The metabolism of Heshuxiaoji pills in vivo is mainly oxidation,glucuronidation and methylation metabolism.This study will lay the foundation for the pharmacokinetic and pharmacodynamic study of Heshuxiaoji pills.