【摘要】 目的建立人血浆中替米沙坦浓度的HPLCMS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,HPLCMS分离、分析。色谱系统ShimadzuODS柱(150mm×46mm),流动相甲醇001mol/L醋酸铵溶液(70∶30,v/v),流速10ml/min,柱温30℃。质谱检测方式SIM。结果替米沙坦的线性范围为05～400ng/ml(r=09998),最低检测浓度达01ng/ml,提取回收率大于80%。受试制剂及参比制剂的生物半衰期分别为(197±30)h和(202±36)h,达峰时间分别为(14±04)h和(16±06)h,峰浓度分别为(1739±304)ng/ml和(1782±355)ng/ml。受试制剂的相对生物利用度为(1012±130)%。结论本法适用于替米沙坦的含量测定,统计学结果表明两种制剂具有生物等效性。更多还原

【Abstract】 AIM:To established an HPLC-MS method 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 analysis was carried out on a Shimadzu VP-ODS column(150 mm×4.6 mm ID,packed with 5 μm C 18 Silica RP particle)at 30 ℃.The mobile phase consisted of methanol-0.01 mol/L ammonium acetate(70∶30,v/v) with the flow rate of 1.0 ml/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 cross over design was performed on 20 healthy volunteers.In the two study periods,a single 40 mg dose of each capsule was administered to each volunteer.RESULT:The linear calibration curve was obtained in the range of 0.5～400 ng/ml(r=0.9998).The detection limit of telmisartan in plasma was 0.1 ng/ml.The average recovery was more than 80%.c max of telmisartan in plasma for the test and reference formulations are(173.9±30.4)and(178.2±35.5)ng/ml at (1.4±0.4) and (1.6±0.6) h,respectively.t 1/2 is (19.7±3.0) and (20.2±3.6) h respectively.The relative bioavailability of the test formulation was(101.2±13.0)%.CONCLUSION:The two formulations are bioequivalent.更多还原