大鼠血浆中白藜芦醇衍生物(BTM-0512)药代动力学研究

Pharmacokinetic studies of resveratrol derivative(BTM-0512)in rat plasma

目的:建立 RP-HPLC 法测定大鼠血浆中白藜芦醇衍生物3,5,4'-O-三甲基白藜芦醇(BTM-0512)浓度的方法并进行药代动力学研究,为该化合物的进一步开发提供实验依据。方法:取血浆样品,以乙腈沉淀蛋白,用 Hypersil C_(18)柱(5 μm,250 mm×4.6 mm)分离,己烯雌酚为内标,乙腈-水(65:35)为流动相,流速1.0 mL·min^(-1),检测波长319 nm。结果:BTM-0512的线性范围为0.01～10.0μg·mL^(-1),r>0.999;日内、日间精密度 RSD 小于10.0%;相对回收率在98.2%～101.3%之间,最低检出限为0.005μg·mL^(-1),最低定量限为0.01μg·mL^(-1)。结论:本方法灵敏度高,操作简便、准确,经方法学确证和稳定性评价,可用于大鼠血浆中 BTM-0512的测定及药代动力学研究。

Objective：To develop an RP - HPLC method for the determination of resveratrol derivative 3,5,4′ - O -trimethylresveratrol （BTM -0512） in rat plasma and to study the pharmacokinetic profile of BTM -0512 in rats. Method：Plasma samples were treated with acetonitrile to deposit proteins, and samples were then analyzed by HPLC on a Hypersil C18 column （ 5μm,250 mm× 4.6 mm） using a acetonitrile - water （ 65： 35 ） mixture solvent as the mobile phase at a flow rate of 1 mL · min^-1. The column effluent was monitored by UV detector at 319 nm and diethylstilbestrol was used as the internal standard. Results：Calibration curves of 3,5,4′ - O - trimethylresveratrol in rat plasma at concentrations ranging from 0.01 to 10.0 μg · mL^-1 were excellent linearity with intra - and inter - day precision of RSD 〈 10. 0% and accuracy in the range 98.2% - 101.3%. The lower limit of detection and quantification were 0. 005 μg · mL^-1 and 0.01 μg · mL^-1 , respectively, in plasma. Conclusion： The validated method is quick, accurate, and has been successfully applied to study the pharmacokinetic characteristics of BTM - 0512 in rats.