高效液相色谱法测定小鼠血浆中1,3-二苯-1,3-丙二酮及其药代动力学研究  

HPLC determination of 1,3-diphenyl-1,3-propanedione in mouse plasma and its application to pharmacokinetic study

作　　者：田寒梅[1] 崔蓉[1] 何月莹[1] 吕艳[1] 张宝旭[1] 

机构地区：[1]北京大学公共卫生学院,北京100191

出　　处：《中国卫生检验杂志》2010年第5期953-955,962,共4页Chinese Journal of Health Laboratory Technology

基　　金：重大新药创制专项(2009ZX09103-007)

摘　　要：目的:建立小鼠血浆中1,3-二苯-1,3-丙二酮(1,3-diphenyl-1,3-propanedione,DPPD)的高效液相色谱测定法,应用该方法测定DPPD在小鼠体内的药代动力学参数,并为DPPD的临床应用提供依据。方法:采用正交试验设计法优化小鼠血浆样本的前处理方法,Symmetry C18色谱柱分离,保留时间定性,内标法定量。雄性ICR小鼠灌胃给予DPPD,不同时间点内眦取血,测定DPPD的经时血药浓度。Thermo Kinetica4.4.1软件计算相应的药代动力学参数。结果:小鼠血浆中DPPD浓度在0.05μg/ml～20μg/ml范围内线性关系良好(r>0.99);加标回收率为91.7%～102.7%。血浆样品在-80℃冰箱中至少可保存15 d。主要药代动力学参数为:t1/2=3.24±0.78 h,Tmax=2.50±0.42 h,Cmax=1.30±0.84μg/ml,AUC0～∞=6.63±2.80 h.μg/ml。结论:该方法准确、灵敏,适用于DPPD小鼠体内药代动力学研究。Objective：To develop the HPLC analytical method for determination of 1,3-diphenyl-1,3-propanedione（DPPD） in mouse plasma and apply to the pharmacokinetic study of DPPD.Methods：Optimization on the sample pretreatment technique with orthogonal array design was investigated.DPPD in mouse plasma was extracted and separated by Waters SymmetryC18 column after extraction.Retention time was used for qualitative analysis and internal standard method for quantitative analysis.Male ICR mice were dosed with DPPD 500 mg/kg via oral gavage.Blood samples were collected from the rhanters of mice as scheduled.The main pharmacokinetic parameters were calculated by Thermo Kinetica4.4.1 software.Results：Calibration curve of DPPD in mouse plasma was linear in the range of 0.05 μg/ml～20 μg/ml（r〉0.99）.The recoveries of DPPD were between 91.7% and 102.7%.The main pharmacokinetic parameters of DPPD were as： t1/2=3.24±0.78 h,Tmax=2.50±0.42 h,Cmax=1.30±0.84 μg/ml,AUC0～∞=6.63±2.80 h·μg/ml.Conclusion：The method is accurate and precise.The assay is suitable for pharmacokinetic study of DPPD in mouse.

关 键 词：1 3-二苯-1 3-丙二酮 小鼠 血浆 高效液相色谱法 药代动力学 

分 类 号：O657.72[理学—分析化学]