论文部分内容阅读
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 high performance liquid chromatography (UPLC) method for the determination of paeonol in plasma of rats with hepatocellular carcinoma and to study the pharmacokinetics of paeonol in rats after intragastric administration. Methods: The rats were divided into 3 groups and given high, medium and low doses of 259.2, 194.4, 129.6 mg.kg-1 paeonol respectively by single gavage. Blood samples were taken at different time points after administration, and plasma concentrations were determined by UPLC. C18 column (2.1 mm × 100 mm, 1.7 μm) was used. The mobile phase was methanol-water (70:30) at a flow rate of 0.3 mL · min-1. The detection wavelength was 274 nm and the column temperature was 25 ℃. Results: The linear range of standard curve of paeonol in plasma samples was 0.323 ~ 41.4 mg.L-1, r = 0.999 9. The plasma concentration data were processed with WinNonlin software. Paeonol in blood samples of rats with liver cancer The concentration-time course accorded with the two-compartment model. The AUC and Cmax increased significantly with the increase of the dose. The Tmax, T1 / 2β and CL did not change obviously with the dose increasing. Conclusion: The method is simple, rapid and reproducible. It is suitable for pharmacokinetics of paeonol in rat model of hepatocellular carcinoma. There were some differences in the pharmacokinetic parameters of pawpaw with different doses after intragastric administration of liver cancer model rats.