Study of pharmacokinetics of aristolochic acid I and II in rats

Objective: To develop an HPLC method for determination of the plasma concentration of aristolochic acid I (AA I) and aristolochic acid II (AA II) and study their pharmacokinetics in rats. Method: The plasma samples were extracted with acetonitrile. The analysis involved a C18 column as stationary phase and methanol, water and acetic acid as mobile phase. The flow rate was 1.0 mL·min^-1, the UV detection wavelength was 315 nm. After a single intravenous dose of 5 mg·kg^-1 AA in rats, the pharmacokinetic parameters were estimated. Result: The calibration curve of AA I was linear over the range from 0.056 mg·L^-1 to 56.3 mg·L^-1 with a correlation coefficient of 0.9997. The mean recovery rate was 88.7%. The RSD of within-day and between-day were all less than 8%. And the calibration curve of AA II was linear over the range from 0.192 mg·L^-1 to 11.52 mg·L^-1 with a correlation coefficient of 0.9989. The mean recovery was 85.8%. The RSD of within-day was less than 3% and between-day was less than 10%. The main pharmacokinetic parameters were estimated to be as follows: CL = (0.010 ± 0.003) L·min^-1·kg^-1, t_1/2α = (8.2 ± 1.7) min, t_1/2β = (79.6 ± 28.5) min for AA I; CL = (0. 003 ± 0.001) L·min^-1·kg^-1, t_1/2α = (56.7 ± 38.1) min, t_1/2β (209.3 ± 37.9) min for AA II. Conclusion: The established HPLC method is simple and sensitive to determine the concentration of AA I, AA II and the metabolite of AA I in rat plasma. From the result of animal's test, we can find that AA I was quickly eliminated from plasma, the elimination of AA II and Aristololactam-the metabolite of AA I - were slower than that of AA I.