Studies On Toxicokinetics And Tissue Residue Of Anagyrine In Rats

The ion-pair liquid chromatographic (IPLC) method were established in this paper for determining the concentrations of anagyrine in rat plasma, liver, kidney and brain in rats. The sample anagyrine of plasma was extracted with chloroform after basificated by with 25% ammonia, and evaporated at temperature of 65℃.then it was dissolved by methanol before determined by IPLC. The chromatographic conditions were as follow HYP ODS column ( 4.6×200mm , 5μm ) at a temperature of 30℃, the mobile phase consisted of water(containing 0.75g SDS,3mLphosphoric acid and 4.5mL tri-ethylamine, adjusted to pH 3.0 ) -acetonitrile-isopropyl alcohol(1500:200:150,in volume ratio ).Mobile phase flow rate was 1.0 ml·min-1 , UV detection wavelength was 309 nm,the detection limits of anagyrine was 10 μg·L^-1 (S/N=3). The Results showed that linear ranges of anagyrine was 60²000μg·L^-1 and the correlation coefficient was 0.9993. The average absolute recovery of anagyrine was 85.53% and the relative recovery was 101.03%. The RSD of inner-day and intra-day were all less than 6.5%. Therefore,this one of the simple, reliable, accurate and sensitive method and suitable for determining anagyrine in rat plasma and for researching distribution of anagyrine in liver, kidney and brain. Following administration of a Single dose of 6.82mg/kg ?b?w anagyrine to rats,blood was taken at 0.5,1.5,2.5,5,10,20,40,60,90,120,240,360,480,600,720 min. Anagyrine concentration of plasma,liver ,brain and kidney were measured by RP-HPLC and concentration-time data were analyzed with a DAS Ver.1.0 pharmacokinetics software. The results indicated that the plasma profiles of Anagyrine in rats conform to one-compartment model after oral administration Toxicokinetics equation is in plasma C=1290.86[e^-0.005t- e^-0.094t],the toxicokinetics parameters were: T_max 40min,C_max 1101.54μg/L,T_1/2ka 7.39min,T_1/2 130.82min,AUC 219696.10μg/L.min,V_d/F 13.94L/㎏ , CL_/F 0.074L/min/ ㎏ . Toxicokinetics equation in liver is C=10727.06[ e^-0.0001t-e^-24570.10t ] ,the pharmacokinetics parameters in liver were: T_max 2.5min,C_max 12095.84μg/L,T_1/2 118.55min,T_1/2ka 0.000min,AUC 1807361.08μg/L.min,V_d/F 15.256L/㎏,V_1/F 0.0017 L/㎏,CL_/F 0.009 L/min/㎏; Toxicokinetics equation in kidney is C=21887.921[e^-0.006t-e^-0.043t];the pharmacokinetics parameters in kidney were: Tmax 60min,Cmax 13747.80μg/L,T_1/2 113.34min,T_1/2ka 16.19min,AUC 3033978μg/L.min,V_d/F 16.193L/kg,CL_/F 0.005L/min/㎏; Toxicokinetics equation in brain is C=21887.921[e-^0.006t-e^-0.043t], the pharmacokinetics parameters in brain were Tmax 20min, Cmax 1260.09μg/L, T1/2 142.05min, T1/2 ka 16.90min, AUC 319068.95μg/L.min, Vd/F 9.82L/kg,CL/F 0.048L/min/㎏. After oral administration., Anagyrine can assimilate and eliminate quickly, can distribute extensively however accumulation time in body is short.