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OBJECTIVE To develop a HPLC method for the determination of plasma concentration of oridonin (ORI) and study the pharmacokinetics of ORI in mice. METHOD Blood was sampled from mice which were injected ORI by 10 mg x kg(-1) at different time intervals, and the concentration of ORI was determined by HPLC. The pharmacokinetic parameters were accessed by 3P97. RESULT The calibration curve was linear (r = 0.998 7) within the range of 0.202-20.0 mg x L(-1) for ORI in plasma. The average recoveries were more than 93%. The within-day and between-day precisions were no more than 9%. After i.v. oridonin in mice, the plasma concentration-time course fitted well to two-compartment model. The pharmacokinetic equation was C = 16.192 5e(-0.554 6t) + 5.475 7e(-0.016 3t). The pharmacokinetic parameters were below: t1/2alpha 1.249 9 min, t1/2beta 42.638 4 min, K21 0.152 3 min(-1), K12 0.359 3 min(-1), K10 0.0592 min(-1), AUC 366.035 0 microg x min x mL(-1), CL 0.0273 L x min(-1) x kg(-1), V(c)0.461 5 L x kg(-1). CONCLUSION The method can be used to determine the concentration and to investigate the pharmacokinetics of ORI in mice. ORI was absorbed and distributed very fast in mice. The effect of ORI was rapid. The elimination was the main process.