摘要
目的采用HPLC法同时测定人血浆中哌拉西林/他唑巴坦的浓度,并考察12名健康受试者分别单次静脉滴注注射用哌拉西林钠/他唑巴坦钠(2 g/0.5 g、3 g/0.75 g和4 g/1 g)后的人血浆中药动学行为。方法血浆样品经乙腈沉淀蛋白,以茶碱为内标,二氯甲烷提取去杂质,水相进样,采用梯度洗脱的方式同时测定哌拉西林/他唑巴坦,经Capcell Pak MG C18柱分离,220 nm波长检测。结果哌拉西林的血浆样品线性范围为0.4～400μg.mL-1,他唑巴坦的为0.4～100μg.mL-1;方法提取回收率为92.5%～97.4%,日内和日间精密度均小于12.2%。对3个剂量组的Cmax、AUC0-t进行相关性分析,他唑巴坦的相关系数分别为0.898和0.893,哌拉西林的分别为0.900和0.909。结论采用HPLC法同时测定哌拉西林/他唑巴坦,准确性好,操作简单;药动学研究结果表明:血浆中哌拉西林/他唑巴坦体内动力学行为符合线性药动学,不同剂量组性别间的药动学参数差异无统计学意义。
Objective A simple and rapid high-performance liquid chromatographic method has been developed and validated for the simultaneous determination of piperacillin/tazobactam in human plasma.This study was to assess dose proportionality following a 0.5 h intravenous infusion single doses（2 g/0.5 g、3 g/0.75 g and 4 g/1 g） of piperacillin/tazobactam in Chinese male and female healthy volunteers,and to provide further information on its pharmacokinetics.Methods Plasma samples were deproteinized with acetonitrile followed by extraction of piperacillin/tazobactam with dichloromethane and injection of the upper aqueous phase by using theophylline as internal standard.The analysis was conducted on a Capcell Pak MG C18 column with gradient elution,and the detecting wavelength was 220 nm.Results The method was linear at plasma levels from 0.4 to 400 μg·mL^-1 for piperacillin and from 0.4 to 100 μg·mL-1 for tazobactam.The correlation coefficient for Cmax and AUC0-t of piperacillin/tazobactam for all three doses were 0.898（tazobactam）/0.900（piperacillin） and 0.893（tazobactam）/0.909（piperacillin）.Conclusion The validated method was proved to be simple,sensitive and rapid.Pharmacokinetic analyses confirmed that the pharmacokinetic profiles of piperacillin/tazobactam were linear,predictable.There were no significant differences between the genders in piperacillin/tazobactam pharmacokinetics.
出处
《广东药学院学报》
CAS
2012年第6期598-602,共5页
Academic Journal of Guangdong College of Pharmacy
基金
"重大新药创制"科技重大专项十二五第二批项目(2012ZX09303015)
辽宁省科学技术计划项目(2009412001-4)
