Pharmacokinetic Study Of Qinghaojienue Pill In Rats

Artemisia carvifolia is annual herb,for the ground part of compositae plants of the genus artemisia annua.The main composition artemisinin is a sesquiterpene lactone compound bearing a peroxide bridge structure,with antimalaria,antitumor,antiparasite,anti-inflammatory and immune regulation in pharmacology.The formulation of Qinghaojienue pill is recored in“Dan Xi Xin Fa”volume 2,it is composed of Artemisia annua:Folium Ilicis:Cinnamomi:Verbena officinalis L,and the corresponding ratio of them is 25:5:3:3.The pharmacokinetics of Qinghaojienue Pill in rats was investigated by HPLC-HRMS method.It can provide reliable basis for the rationality of Qinghaojienue pill formulation and the development of new antimalarial compound preparations,in order to overcome some shortcomings of artemisinin,like short half-life,parasite resistance and etc,thus improve the cure rate and reduce the recurrence rate.The HPLC-PDA-HRMS technique was used to analyze and identify the chemical constituents of Verbena officinalis L,Folium Ilicis and Cinnamomi extract respectively in positive and negative two ways.Twenty one compounds including iridoid glycosides,flavonoids,phenylpropanoids,triterpenoids and phenolic diterpenoids were identified,and six of them were not reported in other literatures about Verbena officinalis L.Ten compounds including Phenolic acids,Glycosidics and terpenoids were identified in Folium Ilicis extract.Only two compounds Protocatechuic aldehyde and cinnamaldehyde were identified in the extract of the Cinnamomi.A sensitive and rapid HPLC-HRMS method was developed for the quantitative analysis of artemisinin and applied to the pharmacokinetic study of artemisinin and Qinghaojienue pill in rats plasma after oral administration.In this paper,artemisinin in plasma samples were extracted by precipitiation with acetonitrile added a certain concentration of sodium nitrite and acetic acid,which could avoid the degradation of artemisinin in hemolysis plasma effectively.The sample preparation method was robust,easy to operate for the simple procedures and suitable for high throughput biological sample analysis.The method was linear over the concentration range of 5-500 ng·mL^-1,the lower limit of quantification was 5ng·mL^-1.Intra-and inter-day precision were both less than 15%and accuracy within±13%.After an oral administration of artemisinin or Qinghaojienue pill,the main pharmacokinetic parameters simulated by noncompartment model were as follows:C_max were 233.55±73.15and 1055.34±487.81 ng·mL^-1;t_maxax were 0.32±0.25 and 1.42±1.06 h;the elimination of half-lives t1/2 were 1.21±0.24 and 1.59±1.29 h;AUC0-∞were 541.41±263.09 and 2455.87±1320.12 h·ng·mL^-1;MRT were 2.17±0.57 and 2.31±0.19 h;CL were 0.22±0.09 and0.06±0.04 L·kg·h^-1;Vss were 0.46±0.19 and 0.13±0.08 L·kg^-1.By comparing the pharmacokinetic parameters of the two kinds of dosage regimen,it could be found that Qinghaojienue pill could promote the absorption of artemisinin in rats largely by about 4.5folders,the remarkable reduced Vss indicated that the distribution of artemisinin was changed and it was mainly distrbued in blood,which would be helpful for the antimalarial effect of artemisinin.