Objective: To study on the pharmacokinetic profiles of evodiamine (EVO) and rutaecarpine (RUT) from Euodiae Fructus powder dressing on the foot sole of Japanese big-ear rabbits with vinegar. Method: The Euodiae Fructus powder (1 g·kg-1) was dressed on the foot sole of male Japanese big-ear rabbits with vinegar in 12 h

the blood was taken from the hearts at different time points (0

1

2

3

4

5

6

8

10

12

24 h) after administration.The plasma samples were pretreated by protein precipitation with acetonitrile

and the concentrations of EVO and RUT in rabbit whole blood were determined by LC-MS

taking Phenomenex Gemini C18 column (4.6 mm×150 mm

5 μm) with mobile phase of acetonitrile-5 mmol·L-1 ammonium formate aqueous solution (62:38)

flow rate was 0.4 mL·min-1

column temperature was 25℃.Tryptanthrin (TRY) was adopted as the internal standard

electrospray ionization (ESI) was applied and operated in positive ionmode

quantification was performed by multiple reaction monitoring (MRM).The main pharmacokinetic parameters were calculated by PKSolver 2.0 according to non-compartment model. Result: The t1/2 of EVO and RUT were(18.55±7.98)

(20.15±1.06) h

Tmax were 5

4 h

Cmax were (4.68±0.34)

(9.76±1.05) μg·L-1

AUC0-t were (58.18±5.46)

(155.38±13.91) μg·L-1·h

AUC0-∞ were (101.46±23.34)

(300.32±36.22) μg·L-1·h

MRT0-∞ were (27.63±9.34)

(31.25±1.47) h. Conclusion: EVO and RUT can be absorbed into the blood through the skin of Japanese big-ear rabbits

and the drug concentration can be maintained within 24 h after withdrawal

which provides the experimental basis for point-application of Euodiae Fructus.