The Metabolism Study Of Alismatis Rhizoma In Vivo Using UHPLC-QT Of-MS

Alismatis Rhizoma(AR)is a traditional Chinese medicine with a long history and has been used for the treatment of nephritis edema,dysuria,and dizziness.In modern pharmacological study,it was found that the triterpenes in AR can lower serum lipids and reduce atherosclerosis.AR can be used for a long time because existing safety evaluation studies have shown that it has minimal kidney and liver toxicity.However,there are few reports about the metabolism of AR in vivo.Therefore,we developed an ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry method,which was based on the characteristic ions of established database of knwon triterpenes.It was used to analyze the major metabolites in rat after oral administration of three representative standards and Alismatis Rhizoma extracts(ARE).Method:1.Study on metabolism of three triterpenes standards of AR in vivoThe triterpenes of AR can be divided into three types according to their characteristic ions.Type I tritepenes represented by alisol B-23 acetate with characteristic ions of m/z 383.3 and 339.3,type II tritepenes represented by alisol C-23 acetate with characteristic ions of m/z 353.3 and type III tritepenes represented by alisol F with characteristic ions of m/z 381.3 and 339.3,respectively.Firstly,the plasma,bile,urine and feces samples of rats were collected after oral administration of the standards of triterpenes.Then,based on UHPLC-QTOF-MS/MS,the chromatography separation was performed on an Ultimate-XB C18 column with the mobile phase of 0.1% formic acid aqueous solution and acetonitrile,and the flow rate was 0.3 m L/min.Data acquisition was performed in positive ionization mode in mass spectrometry analysis.2.Study on metabolism of ARE in vivoBased on the in vivo metabolism of triterpene standards of AR,the in vivo metabolism of ARE was studied using the same method.Result:1.For the in vivo metabolism study of triterpene standards in AR,30 components including prototype compounds and 29 metabolites has been found for alisol B-23 acetate.24 metabolites except prototype compounds was found for alisol C-23 acetate.26 metabolites were found for alisol F except prototype.2.For the in vivo metabolism study of ARE,233 components,including 85 prototype compounds and 148 metabolites,were identified in plasma,urine,feces and bile samples.Most of metabolites were identified in bile samples,ang only 28 metabolites were identified in the plasma samples.3.For the in vivo metabolism study of triterpenes in AR,the major metabolic pathways include dehydrogenation,hydrogenation,oxidation,deacaylation,sulfation,glucuronidation and combined multiple-step metabolism.Conclusion:The metabolic profile of triterpenes from Alismatic Rhizoma in vivo was characterized by UHPLC-QTOF-MS/MS in this study.It is the first time to study the in vivo metabolism of AR,which not only provides a scientific basis for the study of the bioactive components,but also provides valuable information for the continuous study of the pharmacodynamics and pharmacokinetics.