血清呋喃氟脲嘧啶的反相高效液相色谱测定法及在大鼠体内的药代动力学研究

A REVERSED-PHASE HIGH PERFORMANCE LIQUID CHROMATO GRAPHIC DETERMINATION OF FTORAFUR IN SERUM AND ITS PHARMACOKINETIC STUDY IN RATS

本文报道呋喃氟脲嘧啶(FT-207)血清浓度的反相高效液相色谱测定法。固定相为Shim-packCLC-ODS柱(0.15m×6.0φ),流动相为定时程序控制的甲醇溶液,检测波长254nm。样品用甲醇沉淀蛋白,取上清液20ul直接进样。最低检测浓度为0.03μg/ml,标准曲线的线性范围为0.03～132.0μg/ml(r=0.99997)。用本法测定了9只大鼠口服FT-207后的血清浓度,其药时曲线符合一室开放模型。用残数法算得主要药代学参数为k(?)=1.2883±1.0972h^(-1),k_e=0.0767±0.0179h^(-1),tal/2=0.77±0.37h,tel/2=9.42±1.86h,t_p=2.88±1.02h,C_(max)=83.56±11.87μg/ml,AUC=1659.43±258.48μg.h/ml。

A reversed-phase high performance liquid chromato graphy for determination of ftorafur (FT-207) in rat scrum is pre sented.A Shim-pack CLC-ODS (C18) Column was used with a mobi le phase containing variable concentration of methanol which was controlled dy time program.The supernatants of protein-precipitated rat serum diluted 10-fold with methanol were directly injected into the chromatographic system and detected at 254 nm.The injection volume was 20 μl. The measurable lowest concentration was 0.03 μg/ml and the standard curve was linear over the concentration range of 0.03-132.0μg/ml(r=0.99997) The pharmacokinetic study of FT-207 in nine rats is also described.75 mg FT-207/kg was given to rats, and their serum concentrations were measured at different intervals.The curve of concentration vs time was fit to onecompartment open model and its pharmacokinetic parameters were: Ka=1.2883± 1.0972h^(-1), Ke=0.0767±0.0179h^(-1), tal/2=0.77±0.37h, tel/2 9.42±1.86h, tp=2.88±1.02h,Cmax=83.56±11.87μg/ml, and AUC=1659.43±258.48 μg. μh/ml.