摘要
目的:建立大鼠血浆中左旋奥拉西坦的HPLC-UV测定方法,比较其在正常大鼠和脑缺血再灌注模型大鼠体内的药代动力学特征的差异。方法:采用茴拉西坦作为内标,HPLC-UV法测定,色谱柱为APS-2 HYPERSIL柱(250 mm×4.6 mm,5μm),流动相为水-乙腈(12:88),流速1.0 mL·min-1,检测波长214 nm,柱温25℃,采用DAS 2.0软件计算药代动力学参数。结果:血浆中左旋奥拉西坦在0.5～100.0μg·mL-1范围内线性关系良好(r2=0.996 8),方法的提取回收率、精密度、准确度和稳定性均符合生物样品的测定要求。正常对照组大鼠和脑缺血再灌注模型组大鼠的AUC0-t、AUC0-∞、MRT0-t、t1/2z、CLz和Vz具有显著性差异(P <0.05)。结论:该方法灵敏准确、简便、专属性强,适用于左旋奥拉西坦在大鼠体内的药代动力学研究,脑缺血再灌注模型组较正常组大鼠药-时曲线下面积增加,消除速率减慢。
Objective： To establish the HPLC method for the determination of S-oxiracetam in rat plasma and to fgure out the pharmacokinetic differences between the normal rats and the cerebral ischemia-reperfusion model rats. Methods： Aniracetam was used as internal standard. The concentrations of S-oxiracetam in rat plasma were measured by HPLC-UV, which was performed on a APS-2 HYPERSIL column （250 mm × 4.6 mm, 5 μm） with the mobile phase of water-acetonitrile （12 ： 88） at a fow rate of 1.0 mL·min-1. The detection wavelength was set at 214 nm and the column temperature was 25 ℃. The pharmacokinetic parameters were calculated by DAS 2.0 software. Results： The calibration curve of S-oxiracetam was linear in the range of 0.5 – 100.0 μg·mL-1 （r^2 = 0.996 8）. The mean recoveries, precision, accuracy and the stability were in line with the biological sample measurement requirements. The AUC0-t, AUC0-∞, MRT0-t, t1/2z, CLz and Vz of S-oxiracetam in normal rats were signifcantly different from those in cerebral ischemia-reperfusion model rats. Conclusion： The method was proved to be sensitive, accurate, simple and had strong specificity, which was suitable for the pharmacokinetic study of S-oxiracetam. Compared with normal group rats, the AUC of S-oxiracetam increased and the elimination rate of S-oxiracetam slowed down in cerebral ischemia-reperfusion model rats.
作者
利玲
胡秀
利莉
LI Ling;HU Xiu;LI Li(Huangshi Central Hospital,Affliated Hospital of Hubei Polytechnic University,Edong Healthcare Group,Huangshi 435000,China;Hubei Key Laboratory of Kidney Disease Pathogenesis and Intervention,Huangshi 435000,China)
出处
《中国药物应用与监测》
CAS
2018年第5期270-274,共5页
Chinese Journal of Drug Application and Monitoring
关键词
左旋奥拉西坦
高效液相色谱法
脑缺血再灌注
药代动力学
S-oxiracetam
High performance liquid chromatography
Cerebral ischemia-reperfusion
Pharmacokinetics
