尼麦角林在大鼠体内的药代动力学研究

Study on pharmacokinetics in rats of nicergoline for injection

目的:进行尼麦角林在大鼠体内的药代动力学研究。方法:采用甲醇沉淀蛋白进行血浆样品预处理,以 HPLC 法测定大鼠血浆中尼麦角林代谢物1-MMDL 的浓度。色谱柱为 Hypersil C_(18)柱(250 mm×4.6 mm,10μm),流动相为0.03 mol·L^(-1)磷酸二氢钠-甲醇-三乙胺(69:31:0.8,磷酸调节 pH 至3.5±0.1),流速1.0 mL·min^(-1),检测波长228 nm。结果:1-MMDL在0.2～4.0 mg·L^(-1)范围内,浓度与峰面积线性关系良好(r=0.9920),检测限为5.0 ng(S/N=3),空白加样回收率及样品加样回收率均大于95%,日内和日间精密度的 RSD 均小于5.0%,大鼠腹腔注射给药后药物体内处置符合二室模型(W=1/C/C)。结论:本文建立的1-MMDL 血药浓度测定方法及所获得的药动学参数,可为尼麦角林相关制剂的临床研究提供参考。

Objective：To investigate pharmacokinetics of nicergoline in rats. Methods： Protein precipitation method with methyl alcohol was applied to purify plasma samples before analysis. The content of 1 - MMDL which was metabolite of nicergoline in rat plasma samples was determined by HPLC. Separation and determination were achieved on a Hypersil ODS C18column（250 mm ×4. 6 mm, 10 μm）. The mobile phase consisted of sodium dihydrogen phosphate（0.03 mol · L^- 1 ）, methyl alcohol and triethylamine （ 69 ： 31 ： 0. 8, adjusted to pH 3.5 ± 0. 1 with phosphoric acid）at a flow rate of 1.0 mL · min^-1. The detective wavelength was 228 nm. Results： The calibration curve was linear（r =0. 9920） within the range of 0.2 -4.0 mg · L^-1 for 1 - MMDL. The detection limit was 5.0 ng （S/N 〉 3 ）. The analytical recovery was more than 95%. within- day and between- day precision RSD were all less than 5.0% （ n = 5 ）. After intraperitoneal injection, the concentration - time curve of 1 - MMDL in rats plasma could be fitted to two -compartment model （W = 1/C/C）. Conclusion： The method for the determination of 1 - MMDL in plasma samples and the pharmacokinetic parameters obtained could provide reference for other correlated dosage forms on clinical study.