The Effect Of Oleanolic Acid In Qingyedan Tablet On The Pharmacokinetic Of Swertiamarin

OBJECTIVE:To establish a HPLC method to study the relationship between swertiamarin and oleanolic acid,to establish a LC–MS/MS method for determination of swertiamarin in rat plasma,and adopted this method to study the pharmacokinetic characteristics of swertiamarin and oleanolic acid in rats,and providing the referred information for further research and development it.METHODS:?1?Established a HPLC method for simultaneous determination the concentration of swertiamarin and oleanolic acid,according to 10:1?based on the concentration in tablet?compatibility in phosphate buffer solution about pH7.4 study the relationship between swertiamarin and oleanolic acid in normal temperature and37?respectively at 0h,1h,1.5h,3h,4h and 6h.?2?SD rats was the research object,using PPT as the sample clean-up procedure,LC-MS/MS is developmented and confirmed for the quantification of swertiamarin in rat plasma.?3?Comparison the pharmacokinetic process of swertiamarin alone and swertiamarin and oleanolic acid mixture at two administration forms of oral?swertiamarin 20 mg/kg,oleanolic acid 2mg/kg?and intravenous administration?swertiamarin 2 mg/kg,oleanolic acid 0.2mg/kg?..RES?LT:?1?The method developed was suitable for research the relationship between swertiamarin and oleanolic acid.According to 10:1 compatibility in phosphate buffer solution about pH7.4,swertiamarin and oleanolic acid were not interact at room temperature and 37?respectively at 0h,1h,1.5h,3h,4h and 6h.?2?LC-MS/MS was developed and confirmed for the quantification of swertiamarin in rat plasma,this method exhibited good specificity,high sensitivity,precision and accuracy well,and has a satisfactory matrix effect,high recovery rate too.The validated results of the methodology showed that the new method was appropriate for determining of swertiamarin.?3?After oral administration of swertiamarin alone,C_maxax was 1222.9±623.8?g/L,AUC_0-?was 3262±1665?g/L.h,CLz was 7.558±3.486L/h/kg,T_1/2 is 0.939±0.313h,after oral administration of swertiamarin and oleanolic acid mixture,C_max was 839.7±488.78?g/L,AUC_0-?was 2246±1234?g/L.h,CLz was10.82±4.271L/h/kg,T_1/2 was 1.009±0.397h,after intravenous administration of swertiamarin alone,C_max was 11079±2463?g/L,AUC_0-?was 4002±1035?g/L.h,CLz was 0.53±0.14L/h/kg,T_1/2 was 1.25±0.42h,after intravenous administration of swertiamarin and oleanolic acid mixture,C_max was 10576±2034?g/L,AUC_0-?was3381±712?g/L.h,CLz was 0.61±0.12L/h/kg,T_1/2/2 was 0.90±0.17h.Compared the pharmacokinetics of swertiamarin alone with swertiamarin mixture of oleanolic acid of oral administration,we found that oleanolic acid has a certain degree of influence on swertiamarin.Compared male and female,we found that the absorbtion of female rat significant higher than male,While,there was no significant difference of intravenous?2 mg/kg?.The result inferred that oleanolic acid is likely effect the pharmacokinetics of swertiamarin at the phase of absorbtion,gender may effect the absorbtion of swertiamarin.CONCLUSION:Swertiamarin and oleanolic acid without interaction in vitro.Developed a stable and reliable LC–MS/MS method for the quantification of swertiamarin in rat plasma.Oleanolic acid was likely effect the pharmacokinetics of swertiamarin a certain degree of oral administration,gender has difference.This study will help guide the follow-up absorption and metabolism research to swertiamarin.