微透析结合HPLC-ECD测定头孢他啶在大鼠血中含量及其药动学研究

Pharmacokinetic analysis of ceftazidime in rat using microdialysis coupled with high-performance liquid chro-matography and electrochemical detection

目的研究头孢他啶在大鼠血中的药动学。方法采用血液微透析技术结合高效液相色谱-电化学检测法(HPLC-ECD),以甲醇-0.25mol·L-1Na2HPO4(10:90)(pH7.0)为流动相,检测电压为800mV,在线分析静脉注射头孢他啶(90mg·kg-1)后大鼠的血药浓度,经过体内回收率校正后,用3P87程序拟合药动学参数。结果头孢他啶在0.1-100.0μg·mL-1内线性关系良好(r=0.9998),所测血药浓度经3P87程序拟合后药-时曲线符合一室模型,t1/2为27.82min,cmax为189.40μg·mL-1,AUC为7603.00μg·min·mL-1。结论本方法操作简便,结果准确,能满足头孢他啶药动学分析的需要,为药动学研究提供了新的方法学上的参考。

OBJECTIVE: To study the pharmacokinetics of ceftazidime in rat blood. METHODS: Blood microdialysis coupled with high-performance liquid chromatography and electrochemical detection was developed to on-line determine the concentration of ceftazidime in rat blood after the treatment of ceftazidime (90 mg&middotkg-1, iv). The mobile phase consisted of methanol-0.25 mol&middotL-1 Na2HPO4(10:90) (pH 7.0) and the detector's voltage was 800 mV. The data obtained after being calculated using the recovery in vivo were dealed with 3P87 program by computer. RESULTS: A good linear relationship of ceftazidime was obtained between 0.1 and 100 ug&middotmL-1(r = 0.999 8). The concentration-time curve of ceftazidime was fitted to one-compartment model, t1/2 was 27.82 min, C max was 189.40 μg&middotmL-1, AUC was 7 603.00 μg&middotmin&middotmL-1. CONCLUSION: This method was simple, highly sensitive and specific for the pharmacokenetic analysis of ceftazidime, it also provides a valuable method for monitoring the drug's concentration in blood.