HPLC-CAD法测定替诺福韦酯类前药ODE-TFV中ODE残留量  

Determination of ODE residual amount in tenofovir ester prodrug ODE-TFV by HPLC-CAD

作　　者：周洁[1] 姜宏[2] 左利民[1] 易红[1] 李卓荣[1] 山广志[1] 

机构地区：[1]中国医学科学院医药生物技术研究所,北京100050 [2]烟台大学化学化工学院,烟台264005

出　　处：《药物分析杂志》2014年第8期1481-1485,共5页Chinese Journal of Pharmaceutical Analysis

基　　金：科技部新药创制重大专项平台(2012ZX09301002-001-019)

摘　　要：目的：建立测定替诺福韦十八烷氧乙基单酯衍生物（ODE-TFV）中十八烷氧乙醇（ODE）含量的高效液相色谱-电喷雾检测器（HPLC-CAD）的方法。方法：采用Agilent ZORBAX XDB-C8柱（4.6 mm×75 mm,3.5μm）,以0.1 mol·L-1醋酸铵缓冲液（pH 4.0）为流动相A,乙腈为流动相B,梯度洗脱,流速约为1.0 mL·min-1,柱温40℃;采用电喷雾检测器（charged aerosol detector,CAD）,雾化室温度30℃,采样频率10 Hz;进样量10μL。结果：本法的线性范围为0.1000~10.00μg·mL-1（r=0.9999,n=6）,最低检测限为50.00 ng·mL-1;最低定量限为100.0 ng·mL-1;方法平均回收率（n=9）为99.8%。结论：本文建立的方法能满足ODE-TFV原料药中ODE残留量监控的需要。Objective： To establish the high performance liquid chromatography- charged aerosol detector（ HPLC-CAD） method for the determination of octadecyloxyethyl（ ODE） in the sample of octadecyloxyethyl- tenofovir（ ODE-TFV）. Methods： Octadecyloxyethyl-tenofovir and ODE were separated on an Agilent ZORBAX XDB-C8column（ 4. 6 mm × 75 mm,3. 5 μm）. The mobile phase was composed of 0. 1 mol·L- 1ammonium acetate buffer（ pH 4. 0） and acetonitrile with gradient elution mode at a flow rate of about 1. 0 mL·min- 1; signals were detected with CAD; nebulization temperature was 30 ℃ and collection frequency was 10 Hz; the injection volume was 10μL and column temperature was 40 ℃. Results： The linear range of the method was 0. 1000- 10. 00 μg·mL- 1（ r =0.9999,n =6）,and the lowest limit of detection was 50.00 ng·mL- 1; LOQ was 100.0 ng·mL- 1; the average recovery（ n = 9） of the method was 99. 8%. Conclusion： The HPLC method established in this paper can satisfy the demand of ODE residual monitoring in ODE- TFV.

关 键 词：抗艾滋病毒药 替诺福韦酯类前药 替诺福韦十八烷氧乙基单酯衍生物(ODE-TFV) 十八烷氧乙醇(ODE)残留量 高效液相色谱法 电喷雾检测器 

分 类 号：R917[医药卫生—药物分析学]