HPLC-MS法研究替米沙坦人体药动学和生物等效性  

Study of Pharmacokinetics and Bioequivalence of Telmisartan in Human Plasma by HPLC-MS Method

作　　者：刘世坤[1] 刘玉兰[1] 彭向东[1] 邹健军[2] 肖大伟[2] 

机构地区：[1]中南大学湘雅三医院药剂科临床药学研究室,长沙41013 [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：《药物分析杂志》2005年第5期519-522,共4页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:建立准确、灵敏的 HPLC-MS 法测定替米沙坦在血浆中的浓度,以研究替米沙坦在健康受试者中的药动学和生物等效性。方法:20例健康受试者单次口服40mg 替米沙坦受试或参比制剂,按规定时间采集肘静脉血,乙腈沉淀处理血样。采用 Zorbax-SB-ODS 柱,乙腈-0.02mol·L^(-1)醋酸胺缓冲液(28∶72)为流动相,HPLC-MS 内标(坎地沙坦,m/z=423.3)法选择性正离子检测法测定替米沙坦(替米沙坦,m/z=515.3)血浆浓度。结果:HPLC-MS 法测定血浆中替米沙坦的最低检测限为0.5ng·mL^(-1),在2-500ng-mL^(-1)范围内线性关系良好;血药浓度测定日内、日间 RSD 均小于10%。测得替米沙坦受试和参比制剂的主要药动学参数 C_(max)(μg·L^(-1))分别为220.70±95.80和233.11±105.52,AUC_(0-96)(μg·h·L^(-1))分别为1908.54±650.43和1986.26±553.24,t_(1/2)(h)分别为24.1±4.2和24.8±3.8;T_(max)(h)分别为1.8±0.6和1.7±0.7。相对生物利用度 F 为95.6%±6.4%。结论:建立的 HPLC-MS 法灵敏、准确,统计分析表明替米沙坦受试和参比制剂生物等效。Objective:To establish an accurate and sensitive HPLC-MS method for the determination of telmisar- tan in plasma and to evaluate its pharmacokinetic parameters and bioequivalence in healthy volunteers.Method:A single oral dose of 40 mg telmisartan test or reference tablets was given to 20 healthy volunteers in two-way cross -over design.The plasma sample were collected at predetermined time points after the administration,which were extracted by acetonitrile.The plasma concentration of telmisartan were determined by HPLC-MS using Zorbax SB -C_(18)(3.5μm,3.0mm×100mm),acetonitrile-0.02mol·L^(-1)NH_4Ac(28:72)as mobile phase,with positive ion SIM detection of telmisartan([MH]^+,m/z=515.3)using kadishatan([MH]^+,m/z=423.3)as the internal reference.Results:The limit of detection of telmisartan was 0.5ng·mL^(-1)and a good linearity was obtained in the range of 2-500ng·mL^(-1) with the established HPLC-MS method.The relative standard deviation of within-day and between-day determination were less than 10%.The main pharmacokinetic parameters after a single oral dose of 40 mg telmisartan of the test or reference tablets were as follows:C_(max)(μg·L^(-1))220.70±95.80 and 233.11± 105.52,AUC_(0-96)(μg·h·L^(-1))1908.54±650.43 and 1986.26±553.24,t_(1/2)(h)24.1±4.2 and 24.8±3.8, T_(max)(h)1.8±0.6 and 1.7±0.7,respectively;the relative bioavailabity of the test to reference tablets was 95.6% ±6.4%.Conclusion:The established HPLC-MS method was shown to be sensitive and accurate.The statistic results shown that test and reference tablets of telmisartan were bioequivalent.

关 键 词：HPLC-MS法 替米沙坦 生物等效性 人体药动学 相对生物利用度 健康受试者 血药浓度测定 离子检测法 药动学参数 统计分析表 单次口服 肘静脉血 沉淀处理 ODS柱 坎地沙坦 血浆浓度 线性关系 制剂 流动相 缓冲液 检测限 RSD 

分 类 号：R155.5[医药卫生—营养与食品卫生学] R972.4[医药卫生—公共卫生与预防医学]