用LC-ESI-MS测定人血浆中替米沙坦的浓度及其药动学和生物利用度研究(英文)  

Determination of telmisartan in human plasma by HPLC mass spectrometry and studies on its pharmacokinetics and relative bioavailability

作　　者：彭向东[1] 邹建军[2] 刘世坤[1] 李兵[1] 王学锋[1] 阳国平[1] 肖大伟[2] 

机构地区：[1]中南大学湘雅三医院临床药学研究室,长沙410013 [2]南京医科大学附属南京第一医院国家药品临床研究基地,南京210006

出　　处：《中国临床药学杂志》2006年第4期200-203,共4页Chinese Journal of Clinical Pharmacy

摘　　要：目的建立测定人血浆中替米沙坦的液质联用方法。方法采用乙腈直接沉淀血浆蛋白后由ODS柱分离，质谱检测器测定。结果该方法的线性范围为2～500μg·L^-1（r=0．9992），方法回收率在95．8％～105．2％之间，日内和日间精密度都〈10％。采用自身对照交叉试验，单剂量分别给予20名男性健康志愿者2种国产替米沙坦片40mg，其主要药动学参数ρmax为（220．70±95．80）和（233．11±105．52）μg·L^-1，AUC0→96为（1908．54±650．43）和（1986．26±553．24）μg·h·L^-1，t1／2为（24．1±4．2）和（24．8±3．8）h；tmax为（1．8±0．6）和（1．7±0．7）h。结论两种制剂间的主要动力学参数无明显差异，为生物等效制剂，其相对生物利用度为（95．6±6．4）％。AIM To establish a new HPLC mass spectrometry method to determine telmisartan in human plasma. METHODS The method involved deproteinating samples with acetonitrile. The samples were separated by ODS column and determined by mass detector. RESULTS The calibration curve of telmisartan was linear within the range of 2 - 500μg·L^-1, with r = 0.999 2. The recovery rate of this method was within 95.8 % - 105.2 %. The relative standard deviations of within day and between day were less than 10%. To study the pharmacokinetic and relative bioavailability of telmisartan tablets , two formulations of telmisartan tablets were given to 20 healthy male volunteers according to a randomized two-way cross-over design. The pharmacokinetic parameters of the two formulations were（220.70 ± 95.80） and （233.11 ± 105.52）μg·L^-1 for ρmax; （1 908.54 ± 650.43） and （1 986.26 ± 553.24） μg·h·L^-1 for AUC0→96; （24.1±4.2） and （24.8±3.8）h for t1/2; （1.8±0.6） and （1.7±0.7）h for tmax respectively. CONCLUSION The statistic analyses showed that there are no significant differences between the ρmax, AUC0→96, t1/2 and tmax values of the two formulations. The relative bioavailability of tablets Ⅰ with respect to tablets Ⅱ are （95.6 ± 6.4） %. Bioequivalance is observed between the two tablets.

关 键 词：替米沙坦 液质联用 药动学 

分 类 号：R96[医药卫生—药理学]