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目的 :建立HPLC测定家犬血浆中萘哌地尔浓度的方法 ,研究大剂量萘哌地尔胶囊在家犬体内的药物动力学。方法 :健康家犬 5只 ,单剂量给予萘哌地尔胶囊 2 0 0mg后 ,在不同时间点从后肢静脉取血 ,血浆样品碱化后经乙醚提取 ,以乙腈 :磷酸盐缓冲液 (pH 6 .5 ) (6 0 :40 )为流动相 ,由ODSC18分析柱分离测定 ,紫外 2 30nm为检测波长 ,维拉帕米为内标。血药浓度数据用 3p97药物动力学程度处理。结果 :线性范围为 10～ 12 0 0ng·ml-1;方法回收率为98 83%～ 10 1 5 0 % ;日间RSD≤ 5 5 6 % ,日内RSD≤ 3 30 %。单剂量给予家犬萘哌地尔胶囊 2 0 0mg后 ,血药浓度随时间变化规律符合一室开放模型 ,T1/2Ke为 1 91～ 4 99h ,Tmax为 1 87～ 3 2 1h ,Cmax为 338 79～ 414 0 4ng·ml-1。结论 :本方法简便、回收率高、重现性好 ,用于大剂量萘哌地尔在动物体内的药物动力学研究 ,切实可行。
Objective: To establish a HPLC method for the determination of naftopidil in plasma of dogs and to study the pharmacokinetics of high-dose naftopidil capsules in dogs. Methods: Five healthy dogs were dosed with naftopidil capsules at a dose of 200 mg. The blood samples were taken from hindlimb venous at different time points. The plasma samples were alkalified and extracted with ether. The samples were eluted with acetonitrile: phosphate buffer (pH 6 .5) (60:40) as the mobile phase by ODSC18 analytical column separation and determination of UV2 30nm detection wavelength, verapamil as internal standard. Plasma concentration data were treated with 3p97 pharmacokinetics. Results: The linear range was 10 ~ 1200 ng · ml-1. The recovery rate was 98 83% -10 10 0%. The intraday RSD was less than 556%. The intraday RSD was less than 30%. The single-dose administration of naftopidil capsules in dogs showed that the change of plasma concentration with time was in agreement with the open-chamber model. The T1 / 2Ke ranged from 91 to 499 hours, the Tmax ranged from 87 to 321 and the Cmax was 338 79 ~ 414 0 4ng · ml-1. Conclusion: The method is simple, high recovery, good reproducibility, and it is feasible and feasible to study the pharmacokinetics of high dose naftopidil in animals.