HPLC-荧光法研究阿德福韦前药的大鼠组织分布  

HPLC-fluorescence study on tissue distribution of adefovir prodrugs in rats

作　　者：黄丽华[1,2] 刘志勇[1,2] 罗婵[1,2] 母昭德[1] 

机构地区：[1]重庆医科大学药学院,重庆400016 [2]重庆市高校药物工程研究中心,重庆400016

出　　处：《药物分析杂志》2011年第4期637-640,共4页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:建立大鼠组织中阿德福韦(PMEA)含量测定的柱前衍生化HPLC-荧光检测法,研究新型阿德福韦前药M1、M2在Wister大鼠组织中的分布情况。方法:Benetnach C18(150 mm×4.6 mm,5μm)色谱柱,柱前衍生化;流动相A:含2%乙腈的25 mmol·L-1磷酸二氢钾缓冲溶液(5 mmol·L-1氢氧化四丁基铵,pH 6.0),流动相B:含65%乙腈的25 mmol·L-1磷酸二氢钾缓冲溶液(5 mmol·L-1氢氧化四丁基铵,pH 6.0),梯度洗脱;流速1.0 mL·min-1;柱温35℃;荧光检测波长为λex 236nm和λem 420 nm。以泰诺福韦(PMPA)为内标,测定Wister大鼠肝、肾中的药物浓度,比较新型前药M1、M2与阿德福韦酯(ADV)的组织分布特点。结果:组织匀浆中PMEA线性关系、最低检测限、准确度、精密度均符合分析要求。大鼠肝组织中药物浓度:M2>M1>ADV,肾组织中药物浓度:ADV>M1>M2。结论:该方法准确、稳定,灵敏度高,可用于PMEA的检测及药动学研究。在大鼠组织中M2比M1和ADV具有更强的肝靶向性和更弱的肾靶向性,具有继续研发的价值。Objective：To establish a pre-column derivatization HPLC-fluorescence method for the determination of adefovir（PMEA） in rat＇ s tissues,and study the tissue distribution of new adefovir prodrugs in Wister rats.Methods： Pre-column derivatization;A Benetnach C18（150 mm×4.6 mm,5 μm） column was used.Mobile phase A,2% acetonitrile in 25 mmol·L-1 potassium dihydrogen phosphate buffer with 5 mmol·L-1 TBAOH（pH 6.0）;mobile phase B,65% acetonitrile in 25 mmol·L-1 potassium dihydrogen phosphate buffer with 5 mmol·L-1 TBAOH（pH 6.0）,gradient elution.The flow rate was 1.0 mL·min-1,and the column temperature was 35 ℃ with the fuorescence detection set at λex 236 nm and λem 420 nm.Take tenofovir（PMPA） as internal standard,the concentration of PMEA in liver and kidney of Wister rats were tested,and the tissue distribution characteristic of M1,M2 and ADV were compared.Results：All the validation data,such as linearity,detection limit,accuracy and precision,were within the requied limits.Drug concentration in rats＇ liver：M2M1ADV,in kidney：ADVM1M2.Conclusions：This method is accurate,stable and sensitive.It can be used to investigation of PMEA in rats.In tissues of rats,M2 has better targeting to the liver than M1 and ADV and lower targeting to the kidney.The following study of M2 is of value.

关 键 词：阿德福韦(PMEA) 泰诺福韦(PMPA) 阿德福韦酯(ADV) 前药 HPLC-荧光检测法 

分 类 号：R917[医药卫生—药物分析学]