应用离子对-反相高效液相色谱法测定大鼠血浆中阿德福韦酯水解产物  

Determination of metabolites of adefovir dipivoxil in rat plasma samples in vitro by ion pair-HPLC

作　　者：廖沙[1] 刘勤[1] 仲伯华[1] 谢剑炜[1] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850

出　　处：《军事医学科学院院刊》2005年第2期148-151,198,共5页Bulletin of the Academy of Military Medical Sciences

摘　　要：目的:建立一种快速、简单的测定大鼠血浆中阿德福韦酯水解产物阿德福韦单特戊酸甲基酯和阿德福韦的离子对反相高效液相色谱方法。方法:用HypersilODSC18反相柱,乙腈50mmol/L醋酸铵缓冲液(2∶98和50∶50)为流动相,采用梯度洗脱,流速1.0ml/min,紫外检测波长为262nm。结果:测定血浆中阿德福韦浓度的线性范围为1.25～60.0μg/ml(r=0.9999),最低检测限为0.40μg/ml(S/N>3),绝对回收率为76.72%～80.61%。结论:本方法准确,灵敏度较高,重复性好,适于对阿德福韦酯结构类似物进行体外血浆稳定性评估筛选,并可为临床前/临床药代研究提供重要的方法学参考。Objective:To establish a rapid and simple HPLC method for the determination of adefovir dipivoxil and its metabolites in the rat plasma in vitro. Method:The Hypersil ODS column (150 mm×4.6 mm, 5μm) was used as analytical column with a mobile phase consisting of acetonitrile-50 mmol/L ammonium acetate buffer solution containing 2 mmol/L tetrabutylammonium hydrogen sulfate, adjusted to pH 4.0 with acetic acid (2∶98, 50∶50). The flow rate was of 1.0 ml/min with UV detection set at 262 nm. Results: The linear range was 1.25-60.0 μg/ml(r=0.9999)in rat plasma with a detection limit of 0.40 μg/ml (S/N>3). The recovery rate was 76.72%-80.61%. Conclusion: The analytical method has a relatively good sensitivity and reproducibility and it can provide important reference to the preclinical and clinical pharmacokinetic studies.

关 键 词：抗病毒药 阿德福韦酯 离子对-反相高效液相色谱法 质谱法 血浆稳定性 

分 类 号：R96[医药卫生—药理学]