Abstract: AIM:To establish an HPLC method for the determination of aristolochic acid Ⅰ in rat plasma, study the toxicokinetics of aristolochic acid Ⅰ at the three doses adopted in toxicology research and realize the relationship between the exposure level and toxicity.METHODS:Plasma concentrations at different time were determined after single oral administration at the dose of 100, 30 and 10 mg/kg.The data of concentration-time were fitted and the toxicokinetics parameters were calculated by statistical moment then. RESULTS:The limit of quantitation was 0.02 mg/L, the linear range was 0.02 ~ 40.00 mg/L.The average recovery was between 82.4 % ~ 101.2 %.The intraday and inter-day RSD were less than 1.0 %.The parameters of high, middle and low doses were as follows:t_1/2α were (0.8 ±0.4), (0.9 ±0.7) and (1.0 ±0.8) h, t _1/2β were (34 ±19), (133 ±64) and (114 ±50) h, t_max were (0.31 ±0.12), (0.25 ±0.00) and (0.38 ±0.19) h, C_max were (3.0 ±1.7), (1.0 ±0.7) and (1.0 ±0.7) mg/L, AUC_(0-48) were (18 ±3), (18 ±2) and(21 ±5) mg^。L ^-1。h, respectively.CONCLUSION:The method was sensitive, specific and suitable for the analysis of concentrations of aristolochic acid Ⅰ in rat plasma.The absorption of aristolochic acid Ⅰ was quick after single oral administration, and then it was distributed fast and eliminated slowly in the plasma.It was indicated the nonlinear toxicokinetics characteristic of aristolochic acid Ⅰ took place in the studied dose range.

Key words: HPLC, aristolochic acid Ⅰ, single oral administration, toxicokinetics, statistical moment