液相色谱-质谱-质谱联用法测定猕猴血浆中阿德福韦  

Determination of adefovir in monkey plasma by liquid chromatography-tandem mass spectrometry

作　　者：赵丽艳[1] 陈笑艳[1] 张勇[1] 杨汉煜[1] 钟大放[1] 

机构地区：[1]沈阳药科大学药物代谢与药代动力学实验室,辽宁沈阳110016

出　　处：《药学学报》2003年第2期120-123,共4页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目 ( 39930 180 );辽宁省博士启动基金资助项目 ( 0 0 10 2 9)

摘　　要：目的　建立测定猕猴血浆中阿德福韦 (adefovir)的液相色谱 质谱 质谱联用法。方法　取血浆样品 0 2 5mL经甲醇沉淀蛋白后 ,以甲醇 水 甲酸 ( 2 0∶80∶1)为流动相 ,用DiamonsilC1 8柱分离 ,通过电喷雾离子化四极杆串联质谱 ,以选择离子反应监测方式进行检测。用于定量分析的离子反应分别为m z2 74→m z162 (阿德福韦 )和m z2 88→m z 176[内标 ,9 ( 3 膦酸甲氧基丙基 )腺嘌呤 ]。结果　阿德福韦线性范围为 0 0 2～ 4 0 0mg·L- 1 ,最低定量限为 2 0μg·L- 1 ,日内、日间精密度 (RSD)小于 5 8% ,准确度 (RE)在± 4 5 %范围内。在临床前药代动力学研究中 ,应用此法测试了 3只猕猴po给予阿德福韦地匹福酯 (adefovirdipivoxil)后血浆中阿德福韦的浓度。结论　该法操作简便 ,准确 。Aim To develop a sensitive and specific liquid chromatography tandem mass spectrometry (LC/MS/MS) method for the determination of adefovir in monkey plasma. Methods Adefovir and internal standard 9 (3 phosphonylmethoxypropyl)adenine were isolated from plasma by protein precipitation with methanol, then chromatographed by using a Diamonsil C 18 column. The mobile phase consisted of methanol water formic acid (20∶80∶1). Electrospray ionization (ESI) source was applied and operated in the positive ion mode. Selected reaction monitoring (SRM) mode with the transitions of m/z 274→ m/z 162 and m/z 288→ m/z 176 were used to quantify adefovir and the internal standard, respectively. Results The linear calibration curve was obtained in the concentration range of 0 02- 4 00 mg·L -1 . The lower limit of quantitation was 20 μg·L -1 . The inter and intra day precision (RSD) was less than 5 8%, and the accuracy (relative error) was within ±4 5%. The method was successfully used in a pharmacokinetic study of adefovir dipivoxil in monkeys. Conclusion The method is proved to be suitable for pre clinical investigation of adefovir dipivoxil pharmacokinetics, which offers advantages of specificity and simple sample preparation compared with the previously reported methods.

关 键 词：药物浓度 抗病毒药 液相色谱-质谱-质谱联用法 测定 猕猴 血浆 阿德福韦 

分 类 号：R978.7[医药卫生—药品] R969.1[医药卫生—药学]