利用非共价复合物实现对布洛芬分子的手性分析  

Chiral Analysis of Ibuprofen through Non-covalent Complexes

作　　者：古连城 周爱南 陈新 吴芳玲 李建其[2] 余绍宁 周鸣飞 丁传凡 GU Lian-Cheng;ZHOU Ai-Nan;CHEN Xin;WU Fang-Ling;LI Jian-Qi;YU Shao-Ning;ZHOU Ming-Fei;DING Chuan-Fan(Department of Chemistry,Fudan University,Shanghai 200433,China;Shanghai Institute of Pharmaceutical Industry,Shanghai 200240,China;School of Material Science and Chemical Engineering,Institute of Mass Spectrometry,Ningbo University,Ningbo 315211,China)

机构地区：[1]复旦大学化学系,上海200438 [2]上海医药工业研究院,上海200040 [3]宁波大学材料科学与化学工程学院,质谱技术与应用研究院,宁波315211

出　　处：《分析化学》2021年第1期95-102,共8页Chinese Journal of Analytical Chemistry

基　　金：国家自然科学基金项目(Nos.21773035,21803013)资助。

摘　　要：手性药物的检测对于深入了解药物作用机理具有十分重要的意义。布洛芬(Ibuprofen)是常用的临床消炎药物,具有R型和S型两种构型,但其消炎作用却几乎全部由S-布洛芬所提供。本研究建立了一种区分布洛芬手性的方法,将布洛芬对映体与γ-环糊精及BaCl2混合,得到系列非共价复合物,利用捕集离子淌度质谱(Trapped ion mobility spectrometry-time-of-flight mass spectrometry,TIMS-TOF MS)测量各物质的离子淌度(Ion moboility)。采用TIMS-TOF MS成功分离了非对映体离子[γ-CD+R-Ibuprofen+Ba(BaCl)-H]2+与[γ-CD+S-Ibuprofen+Ba(BaCl)-H]^2+,碰撞截面的差值高达0.07 nm^2。此外,实验结果表明,一系列[γ-CD+S-Ibuprofen+Ba(BaCl)-H]^2+的离子淌度谱峰强度分数与其摩尔分数呈线性关系。本方法无需对样品分子进行前处理或化学衍生化,可以快速、高效地分析手性分子。The recognition and discrimination of chirality is of great significance for further understanding the pharmaceutical mechanism of chiral drugs.Ibuprofen is a well-popular clinically used anti-inflammatory drug in the world.However,in R-ibuprofen and S-ibuprofen enantiomers,only S-ibuprofen is responsible for the anti-inflammatory effects.In this work,a novel discrimination method for chiral ibuprofen was investigated.A stoichiometric R-and S-Ibuprofen were mixed withγ-cyclodextrin and barium chloride to obtain the noncovalent complexes in methanol aqueous solution,and the ion mobility of the complexes was measured by trapped ion mobility spectrometry-time-of-flight mass spectrometry(TIMS-TOF-MS).The formed diastereomeric ions of[γ-CD+R-ibuprofen+Ba(BaCl)-H]2+and[γ-CD+S-ibuprofen+Ba(BaCl)-H]^2+ were successfully separated in ion mobility spectra and the collision cross section difference(ΔCCS)reached 0.07 nm^2.Additionally,the experimental data indicated that the fractions of mobility peak intensities for[γ-CD+S-ibuprofen+Ba(BaCl)-H]^2+ and their molar fractions exhibited a great linear relationship.Due to that no complicate pre-treatment or chemical derivation was needed,this method could discriminate chiral molecules rapidly and efficiently.

关 键 词：布洛芬 Γ-环糊精 氯化钡 非共价复合物 手性分析 捕集离子淌度质谱 

分 类 号：O657.63[理学—分析化学] TQ460.72[理学—化学]