基于直链淀粉衍生物手性固定相的高效液相色谱-串联质谱法拆分4种β-受体阻滞剂对映体及其分离机制的探讨  

Chiral separation of four β-blocker enantiomers using high performance liquid chromatography-tandem mass spectrometry based on amylase derivative chiral stationary phases and investigation on their separation mechanism

作　　者：钱哲元 张明勇[1] 李升妮 洪战英[1] 柴逸峰[1] QIAN Zheyuan;ZHANG Mingyong;LI Shengni;HONG Zhanying;CHAI Yifeng(School of Pharmacy,Second Military Medical University,Shanghai 200433,China)

机构地区：[1]第二军医大学药学院,上海200433

出　　处：《色谱》2018年第3期261-267,共7页Chinese Journal of Chromatography

基　　金：国家自然科学基金资助项目(81373376;81673386)~~

摘　　要：建立了以直链淀粉衍生物为手性固定相的高效液相色谱-串联质谱(HPLC-MS/MS)直接拆分普萘洛尔、美托洛尔、阿罗洛尔和卡维地洛4种β-受体阻滞剂对映体的方法。考察了手性固定相的种类、流动相改性剂和添加剂的体积分数、柱温和流速等对4种药物对映体分离的影响。结果表明:在Chiralpak AD-H手性色谱柱上,在正己烷-乙醇-二乙胺(20∶80∶0.03,v/v/v)为流动相、流速0.550 mL/min、柱温40℃的条件下,普萘洛尔、美托洛尔、阿罗洛尔和卡维地洛对映体均达到基线分离,分离度分别为1.37、1.80、2.09和4.70。通过热力学研究及对映体结构分析对拆分机理进行了探讨,发现4种药物对映体的手性拆分均为焓驱动过程,而固定相的手性空腔对不同药物的拆分影响较大。研究结果为β-受体阻滞剂的深入研究提供了参考方法。A high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)method based on amylose derivatives as chiral stationary phases(CSPs)for the chiral separation of four 6-blocker enantiomers(propanolol,metoprolol,arotinolol and carvedilol)was established.The effects of different CSPs,volume fractions of mobile phase modifiers and mobile phase additives,column temperatures and flow rates on the chiral separation of the four 6-blocker enantiomers were evaluated.Baseline separation of the four 6-blockers enantiomers was obtained on a Chiralpak AD-H chiral column using the mobile phase of n-hexane-ethanol-diethylamine(20:80:0.03,v/v/v)at a flow rate of 0.550 mL/min and a column temperature of 40℃.The resolutions of the enantiomers for propanolol,metoprolol,arotinolol and carvedilol were 1.37,1.80,2.09 and 4.70,respectively.The separation mechanism of the four 6-blocker enantiomers was investigated by thermodynamic analysis and enantiomeric structure analysis.The chiral separation was all enthalpy controlled,and the cave structure of the chiral stationary phase played an important role on the separation.The method provides reference for further studies of theβ-blocker enantiomers.

关 键 词：高效液相色谱-串联质谱 直链淀粉衍生物手性固定相 手性拆分 分离机制 6-受体阻滞剂对映体 

分 类 号：O658[理学—分析化学]