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目的研究5-氟尿嘧啶在大鼠血液中的药动学。方法采用血液微透析技术结合高效液相色谱-紫外检测器(HPLC-UV),以体积分数5%甲醇溶液-30 mmol·L-1磷酸二氢钾(pH=7.10)为流动相,流速0.8 mL·min-1,柱温30℃,紫外检测波长254 nm进行实验,分析静脉注射5-氟尿嘧啶(15mg·kg-1)后大鼠的血药质量浓度,经体外回收率校正后,用DAS 2.1.1软件拟合药动学参数。结果5-氟尿嘧啶质量浓度在0.1~40.0 mg·L-1内与峰面积呈良好的线性关系(r=0.999 9),所测血药质量浓度经DAS软件拟合后药-时曲线符合二室模型(W=1/C/C),5-氟尿嘧啶的血浆生物半衰期为(0.38±0.08)h,Clz为(0.82±0.09)L·h-1·kg-1。结论本方法操作简便、快速、准确,能满足5-氟尿嘧啶药动学分析的需要,可用于5-氟尿嘧啶的血药质量浓度监测和药动学研究。
Objective To study the pharmacokinetics of 5-fluorouracil in rat blood. Methods The blood microdialysis technique and HPLC-UV detector were used. The mobile phase consisted of 5% methanol solution-30 mmol·L-1 potassium phosphate monobasic (pH = 7.10) and the flow rate was 0.8 mL · min-1, the column temperature was 30 ℃ and UV detection wavelength was 254 nm. The plasma concentrations of 5-Fluorouracil (15 mg · kg-1) after intravenous injection were analyzed. 2.1.1 software fitting pharmacokinetic parameters. Results The concentration of 5-Fluorouracil showed a good linear relationship with the peak area (r = 0.999 9) in the range of 0.1-40.0 mg · L-1. The measured plasma concentration was fitted by DAS software, (0.38 ± 0.08) h and (0.82 ± 0.09) L · h-1 · kg-1 for 5-fluorouracil in the model (W = 1 / C / C) Conclusion The method is simple, rapid and accurate, and can meet the needs of pharmacokinetic analysis of 5-Fluorouracil. It can be used to monitor the concentration of 5-Fluorouracil and pharmacokinetics.