丹皮酚在肝癌模型大鼠体内的药动学研究

Pharmacokinetic Study of Paeonol in Liver Cancer Model Rat

目的:建立测定肝癌模型大鼠血浆中丹皮酚浓度的超高效液相色谱(UPLC)法,并用于丹皮酚灌胃给药后在大鼠体内的药动学研究。方法:大鼠分成3组,分别单次灌胃给予高、中、低剂量259.2,194.4,129.6 mg.kg-1丹皮酚,于给药后不同时间点采集血样,UPLC测定血药浓度。选用C18色谱柱(2.1 mm×100 mm,1.7μm),流动相甲醇-水(70∶30),流速0.3 mL.min-1,检测波长274 nm,柱温25℃,进样量2.1μL。结果:丹皮酚在血浆样品中标准曲线线性范围为0.323～41.4mg.L-1,r=0.999 9,其血药浓度数据用WinNonlin软件处理,丹皮酚在肝癌模型大鼠体内的血药浓度-时间过程符合二房室模型,AUC,Cmax随给药剂量增加而显著增加,Tmax,T1/2β,CL随给药剂量增加无明显改变。结论:该方法简便,快速,重复性好,适用于丹皮酚在肝癌模型大鼠体内的药动学研究。肝癌模型大鼠灌胃不同剂量丹皮酚后的药动学参数存在一定差异。

Objective： To establish a sensitive ultraperformance liquid chromatography （UPLC） method for determining the plasma concentration of paeonol in liver cancer model rat and to evaluate its pharmacokinetic characteristics. Method： Rats were divided into three groups, a single ig dose of 259.2, 194.4, 129.6 mg ·kg^（-1） paeonol was given respectively. Paeonol was separated on a Cls column with methanol： water （70： 30） as mobile phase. The plasma concentration of paeonol was determined and its pharmacokinetic parameters were calculated by using WinNonlin 5.2. I. Result： The linear range of the method for paeonol was 0. 323-41.4 mg·L^（-1）. The plasma concentration-time course showed two compartment model, with the increased dose, AUC, Cmax has a significant increase, while Tmax, T1/2β, CL have no significant change. Conclusion： The UPLC method for determining paeonol concentration in plasma is simple, rapid, sensitive and suitable for pharmacokinetic study. There are some differences between pharmacokinetic parameters in liver cancer model rats with different dose of paeonol.