文档介绍：中文摘要本研究建立了高效液相色谱法(HPLC)测定生物样本中头孢哌***(CPZ)和他唑巴坦(TB)浓度的方法,对注射用头孢哌***钠他唑巴坦钠(6:1) (CPZ/TB)在健康志愿者体内的药代动力学进行研究,考察其在健康人体内的药代动力学特征,得出主要药代动力学参数,为新药的临床审批以及制定安全、合理、有效的临床用药方案提供依据。取得的主要成果: 1、本研究建立了以HPLC法测定生物样本中CPZ和TB浓度的分析方法学。CPZ的色谱条件:色谱柱:Diamonsil C18(,59in); 流动相:20 mmol·L‘1磷酸二氢钠水溶液():甲醇=65: 35;流速:1 mL·min~;紫外检测波长:254nm。TB的色谱条件:色谱柱: Diamonsil C18(150×,59m);流动相:20mmol·L_磷酸二氢钠水溶液(, mmol·L一的四丁基溴化铵) :乙***=84: 6;流速:1 mL·min~;紫外检测波长为:230nm。此方法具有较高的检测特异性、精密度、灵敏度和可重复性,适用于生物样品中CPZ和TB的定量分析。 2、单次静脉滴注CPZ/TB,各剂量组CPZ和TB的药代动力学参数伍、p、t1,2”t1/21B、Cls基本一致。CPZ和TB的血药浓度随给药剂量增高而升高,。双周期随机自身交叉对照实验证明同时使用TB对CPZ的药代动力学过程无影响。 3、在本研究给药剂量范围内,CPZ和TB的AUC、Cmax与剂量呈线性相关,表明在给药剂量范围内CPZ和TB基本符合线性药代动力学特征。关键词:头孢哌***钠、他唑巴坦钠、药代动力学 ABSTRACT To estabilish an High performance liquid chromatography(HPLC)method to monitor concentrations ofCefoperazone(CPZ)and Tazobactam(TB)in human plasma and urine sample,to assess for ics after adminstration Cefoperazone Sodium and Tazobactam Sodium forIniection (6:1)(CPZ/TB)in healthy volunteers,and toprovide scientific evidence for reasonable guideline forclinical applicaton。 Results and ConeIusion: simple rapid and sencitive analytical method for the determination of CPZ and TB was separation ofCPZ was performed on a Diamonsil C18(1 ,5斗m)column and the mobile phase consisting of(containing 20mmol·L~NaH2P04,pH=)water: methanol(65/35,v/v).The flOW rate was mL·min叫;the detection wavelength was set separation ofTB on a Diamonsil Ct8 column(1 ,5pm).The mobile phase consisting of(containing 20 mmol’mL~NaH2P04 and bromide, pH=)water:acetonitrile(84/16,v/v).The flow rate was 1mL·min“; the detection wavelength was set good validation criteria results ofthe method and sensitivity allowed its use to determine CPZ and TB inhuman plasma and urine sample. drug level increased with the dose ofCPZ/TB,the ic parameters(a,p,tl/2Ⅱ,tl/21B,Cls)of CPZ and TB with all d