UPLC分析大鼠血浆中阿齐沙坦浓度及其初步药代动力学研究  

Plasma Concentration of Azilsartan Determined by Ultra-performance Liquid Chromatography and Its Preliminary Pharmacokinetics in Rats

作　　者：樊玲[1] 李洁[1] 彭兆亮[1] 王雪琦[1] 汪电雷[1] 杨晔[1] 陈亚军[1] 王淑君[1] 

机构地区：[1]安徽中医药大学药学院,安徽合肥230012

出　　处：《安徽中医药大学学报》2017年第1期77-80,共4页Journal of Anhui University of Chinese Medicine

基　　金：国家自然科学基金项目(81473536);安徽省科技攻关计划项目(1301042097);安徽中医药大学校级探索性科研项目(2016ts070)

摘　　要：目的采用UPLC建立大鼠血浆中阿齐沙坦浓度的测定方法,并探究阿齐沙坦在大鼠血浆中初步药代动力学情况。方法选用缬沙坦为内标,色谱柱Kinetex C18(100mm×2.10mm,1.7μm),紫外检测波长254nm,流动相为水-乙腈-冰醋酸(容积比为57∶42∶1),流速0.2mL/min,柱温25℃,进样量2μL,建立在大鼠血浆中阿齐沙坦的分析方法。在此方法的基础上,经大鼠尾部静脉注射阿齐沙坦0.5mg/kg,测定不同时间点其血浆浓度。实验数据运用DAS 2.1软件分析,得其主要药代动力学参数。结果大鼠血浆中阿齐沙坦的线性范围为0.05~12.5mg/L(r=0.999 9),定量下限为0.05mg/L,低、中、高浓度(0.1、1.0、10.0mg/L)的提取回收率分别为(88.6±3.2)%、(86.5±2.2)%、(85.7±1.3)%(RSD<5%),日内、日间精密度RSD不大于10%,准确度在85%~100%范围内。通过DAS 2.1软件拟合,阿齐沙坦的分布半衰期t1/2(α)为(0.39±0.04)h,消除半衰期t1/2(β)为(4.22±0.12)h,药时曲线下面积(AUC0-t)为每小时(53.25±2.46)mg/L。结论本实验建立的UPLC操作快速、简单,且专属性强,适用于阿齐沙坦在大鼠血浆中浓度的分析及其药代动力学的探究。Objective To determine the plasma concentration of azilsartan in rats by ultra-performance liquid chromatography （UPLC）, and to investigate its preliminary pharmacokinetics in plasma. Methods UPLC was performed with valsartan as the internal standard on a Kinetex C18 column （100 mm ×2.10mm, 1.7 μm） with a mobile phase of water-acetonitrile-glacial acetic acid （volume ratio 57： 42： 1） at an ultraviolet detection wavelength of 254 nm, a flow rate of 0.2 mL/min, a column temperature of 25 ℃, and a sample size of 2 μL to establish the method for analyzing azilsartan in plasma. On the basis of UPLC, rats were given tail vein injection of azilsartan 0.5 mg/kg, and the plasma concentration of azilsartan was measured at different time points. The experimental data were analyzed by DAS 2.1 to obtain the pharmacokinetic parameters of azilsartan. Results Azilsartan showed a good linear relationship within the range of 0.05-12.5 mg/L （r=0. 999 9）, with a lower limit of quantification of 0.05 mg/L. The recovery rates of low-, medium-, and high-concentration azilsartan （0.1, 1.0, and 10.0 mg/L） were （88.6±3.2）%, （86.5±.2）%, and （85.7±1.3）%, respectively [-relative standard deviation （RSD） 〈5%]. The RSDs for intra-day precision and inter-day precision were not greater than 10%, and the accuracy ranged from 85% to 100%. The fitting analysis with DAS 2.1 software showed that the distribution half-life （t1/2（α）） of azilsartan was （0.39±0.04） h, the elimination half-life （t1/2（β）） of azilsartan was （4.22± 0.12） h, and the area under the concentration-time curve （AUC0-t） was （53.25±2.46）mg/L per hour. Conclusion The UPLC method established in this experiment is quick, simple, and specific and can be used for the analysis of plasma azilsartan concentration and its pharmacokinetics in rats.

关 键 词：阿齐沙坦 UPLC 血药浓度 药代动力学 

分 类 号：R969.1[医药卫生—药理学]