环糊精键合相拆分和测定人血浆中β-受体阻滞剂对映体  

Enantioseparation and Determination ofβ-Blocker Enantiomers in Human Plasma by Cyclodextrin-bonded Phase by HPLC

作　　者：黄志琴 曾庆丽 李丹[1] 李来生[1] HUANG Zhiqin;ZENG Qingli;LI Dan;LI Laisheng(School of Chemistry and Chemical Engineering,Nanchang University,Nanchang 330031)

机构地区：[1]南昌大学化学化工学院,江西南昌330031

出　　处：《分析科学学报》2024年第3期263-269,共7页Journal of Analytical Science

基　　金：国家自然科学基金(31860469);江西省科技创新平台项目(20192BCD40001)。

摘　　要：本文采用一种新型的桥联双β-环糊精固定相,通过优化色谱条件,实现了常见β-受体阻滞剂卡维地洛、阿罗洛尔和阿替洛尔6种对映体的完全分离,分离度分别为1.6、1.9和1.7。以R-阿普洛尔为内标,建立了一种能同时测定人体血浆中上述6种对映体含量的液相色谱新方法。血浆样品碱化后用乙酸乙酯提取和净化,选择极性有机相体系(乙腈/甲醇/三乙胺/冰乙酸),通过梯度洗脱完全拆分对映体,柱后二极管阵列检测(275 nm),内标法定量。结果表明,在各自质量浓度范围内,6种β-受体阻滞剂对映体波长响应值与含量呈良好的线性关系(R2为0.9923~0.9989)。对映体的检测限(S/N=3)和定量限(S/N=10)分别在0.4~1.5 mg/L和1.5~4.0 mg/L范围内,样品加标平均回收率为85.96%~103.88%,测定结果的日内和日间的相对标准偏差范围分别为1.88%~3.29%和3.02%~5.17%。该方法具有操作简便、结果准确性和手性分离度高等优点,可同时测定多个对映体,提高分析效率,降低测试成本。In this paper,a new type of bridged bis-β-cyclodextrin stationary phase was used to improve the separation selectivity by making full use of its multiple recognition effects such as synergistic inclusion.By optimizing the chromatographic conditions,six enantiomers of commonβ-blockers(carvedilol,arotinolol and atenolol)were completely separated,and the resolutions were 1.6,1.9 and 1.7 respectively.A new HPLC method for simultaneous resolution and determination of the above six enantiomers in human plasma was established with R-aproprolol as internal standard.The alkalized plasma samples were extracted and purified with ethyl acetate,and the polar organic mobile phase(ACN/MeOH/TEA/HOAc)was selected.The enantiomers were completely separated by gradient elution,detected by a diode-array detector at 275 nm,and quantified by an internal standard method.The experimental results showed that the six enantiomers ofβ-blockers had good linear relationship with R 2 of 0.9923-0.9989 within their respective mass concentration ranges.The detection limit(LOD)and quantitative limit(LOQ)of all enantiomers were in the range of 0.4-1.5 mg/L and 1.5-4.0 mg/L,respectively.The average recoveries from plasma samples were 85.96%-103.88%.The RSDs of the determination results were 1.88%-3.29%for intra-day and 3.02-5.17 for inter-day,respectively.This method has the advantages of simple operation,high recoveries,good accuracy and resolution.Simultaneous determination of multiple enantiomers can save analysis time,improve analysis efficiency and reduce test cost.

关 键 词：Β-受体阻滞剂 桥联双β-环糊精液相色谱固定相 手性拆分 对映体定量 人体血浆 

分 类 号：O657.72[理学—分析化学]