LC-MS/MS法研究阿德福韦酯胶囊的人体药动学  

Pharmacokinetic study of adefovir dipivoxil capsules by LC-MS/MS method

作　　者：邱娟[1] 杭太俊[1] 沈建平[2] 张银娣[2] 张喜来[3] 徐中南[3] 张爱民[3] 

机构地区：[1]中国药科大学药物分析室,南京210009 [2]南京医科大学临床药理研究所,南京210029 [3]江苏正大天晴药业股份有限公司,连云港222006

出　　处：《中国临床药学杂志》2006年第5期292-295,共4页Chinese Journal of Clinical Pharmacy

摘　　要：目的建立LC-MS／MS法测定血浆中阿德福韦酯活性代谢物阿德福韦的浓度，并用于健康受试者口服阿德福韦酯（E晶型）胶囊后的药动学研究。方法10名受试者口服阿德福韦酯胶囊后，血浆样品经高氯酸沉淀蛋白，LC-MS／MS法测定阿德福韦的浓度，用3P97程序计算主要药动学参数。结果测定血浆中阿德福韦的最低定量限为0．5μg·L^-1，血药浓度为0．50～150μ·L^-1时质谱响应线性关系良好（r=0．9996）。测得单剂量和稳态时口服10mg阿德福韦酯（E晶型）胶囊后主要药动学参数：ρmax分别为（23．93±6．86）和（38．93±7．52）μg·L^-1，tmax分别为（1．5±0．7）和（1．7±0．5）h，t1／2分别为（8．70±1．56）和（10．57±1．16）h，AUC0→48分别为（292．07±62．75）和（486．78±110．65）μg·h·L^-1。结论该方法灵敏，可用于阿德福韦酯人体药动学研究。AIM To establish a liquid chromatography - mass spectrometry/mass spectrometry （LC-MS/MS） method for the determination and pharmacokinetic study of adefovir in Chinese healthy male volunteers after oral administration of adefovir dipivoxil （ in the patented crystalline type of E） capsules. METHODS Plasma samples were processed with perchloric acid precipitation. Determination was performed on LC-MS detection operated in API-ES positive SRM mode. The major pharmacokinetic parameters of adefovir were calculated with the 3P97 software. RESULTS The limit of quantitation of adefovir in plasma was 0.5 μg· L^-1 and a good linearity was obtained in the range from 0.50 to 150 μg· L^-1（ r = 0.999 6）. The pharmacokinetic parameters after a single oral dose of 10 mg adefovir dipivoxil and at steady state was obtained as follows： ρmax was （23.93 ± 6.86） and （38.93 ± 7.52） μg· L^-1, tmx Was （ 1. 5 ± 0. 7） and （1.7±0.5）h, t1/2 was （8.70± 1.56） and （10.57 ± 1.16） h, AUC0→48 was （292.07 ± 62.75） and （486.78 ± 110.65）μg·h·L^-1, respectively. CONCLUSION The established method is shown to be sensitive and suitable for the pharmacokinetic study of adefovir.

关 键 词：阿德福韦酯 阿德福韦 药动学 LC-MS/MS 

分 类 号：R96[医药卫生—药理学]