替米沙坦胶囊在人体内的药代动力学及生物等效性研究.pdfVIP

替米沙坦胶囊在人体内的药代动力学及生物等效性研究 冯芳*,武洁 中国药科大学药物分析学教研室 南京210009 摘要 目的 建立人血浆中替米沙坦浓度的HPLC-MS 分析方法 用以测定健康受 试者口服替米沙坦制剂后的血药浓度 估算受试制剂和参比制剂的药代动力学参数 评价两 种制剂的生物等效性和相对生物利用度 方法 血浆中加入内标地西泮后 乙酸乙酯提取 HPLC-MS 分离 分析 色谱系统 Shimadzu ODS 柱 (150mm 4.6mm) 甲醇-醋酸铵溶液 0.01 mol/L (70 30 v/v)为流动相 流速 1.0ml/min 柱温30 质谱检测方式 SIM 结果 替米沙坦的线性范围为0.5 400ng/ml r=0.9998 最低检测浓度达0.1ng/ml 提取 回收率 80% 受试制剂及参比制剂的生物半衰期分别为 19.7±3.0h 和20.2±3.6h 达峰时间 分别为 1.4±0.4h 和 1.6±0.6h 峰浓度分别为 173.9±30.4 ng/ml 和 178.2±35.5ng/ml 受试制剂 的相对生物利用度为 101.2±13.0 % 结论 本法简便 准确 灵敏度高 统计学结果表 明两种制剂具有生物等效性 关键词 替米沙坦 HPLC-MS 法 血药浓度 药动学参数 生物等效性 Study of Pharmacokinetics and Bioequivalence of Telmisartan WU Jie , FENG Fang , Jiang Juan-Juan , Tian Yong Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China ABSTRACT AIM: A HPLC-MS method was established for the study of pharmacokinetics and bioequivalence of telmisartan in human body. METHOD: Diazepam was used as internal standard. After adding diazepam, the plasma samples were extracted with ethyl acetate and determined by HPLC-MS. The separation was carried out on a Shimadzu VP -ODS column(150mm×4.6mm i.d., packed with 5m C18 silica RP particle) at 30 .The mobile phase was methanol-0.01mol/L ammonium acetate (70:30,v/v), running at a flow rate of 1.0ml/min. HPLC -MS was performed in the selected ion monitoring(SIM) mode using target ions at m/z 515.6 for telmisartan and m/z 285.5 for diazepam. A randomized crossover design was performed in 20 healthy volunteers. In the two study periods, a single 40 mg dose of each capsule was ad