Abstract: AIM:To establish an HPLC/MS method for simultaneous determination of mesaconitine, aconitine and hypaconitine in rabbit plasma, and study their toxicokinetics in wild aconite poisoned rabbits after hemoperfusion. METHODS:Eight health grownup male Japan big ear white rabbits [the body weight (2. 5 ±0. 2)kg] were intragastrically poisoned by wild aconite liquor 1. 0 mL/kg and the hemoperfusion was given for 2 h at 0. 25 h after poisoning. The blood was taken after poisoned 0. 5, 1, 1. 5, 2, 3, 6, 12, 24 h respectively. The concentrations of mesaconitine, aconitine and hypaconitine in plasma were detected by HPLC/MS. The toxicokinetics parameters were calculated by DAS 2. 0 program. RESULTS:The parameters of toxicokinetics for mesaconitine in wild aconite poisoned rabbits after hemoperfusion were as following: t_max(3. 1 ±0. 8)h, C_max(11. 5 ±2. 1)μg/L, K_a(1. 6 ±0. 9)h, K_e(0.13 ±0. 05)h, t_1/2(5. 9 ±1. 7)h, V/F (85. 4 ±20. 9)L/kg, CL/F (10. 28 ±1. 46) L·h^-1 ·kg^-1. The parameters of toxicokinetics for aconitine were as following: t_max(3. 2 ±0. 5)h, C_max (18. 7 ±5. 5)μg/L, K_a (1. 2 ±0. 4)h, Ke (0.10 ± 0. 03)h, t_1/2(7. 5 ±2. 4)h, V F(2. 7 ±1. 0)L/kg, CL/F(0. 25 ±0. 08)L·h^-1 ·kg^-1. The parameters of toxicokinetics for hypaconitine were as following: t_max(3. 0 ±0. 8)h, C_max(14. 6 ±11. 0)μg/L, K_a(1. 4 ± 1. 2)h, K_e(0. 09 ±0. 03)h, t_1/2(8. 3 ±2. 1)h, V/F (10. 7 ± 6. 9) L/kg, CL/F (0. 85 ± 0. 38) L·h^-1 ·kg^-1. CONCLUSION:The toxicokinetics of mesaconitine, aconitine and hypaconitine in wild aconite poisoned rabbits after hemoperfusion are fitted to the one-compartment model with first-order absorption.

Key words: mesaconitine, aconitine, hypaconitine, hemoperfusion, HPLC/MS, toxicokinetics