甲磺酸多黏菌素E_2组分的色谱分离及质谱裂解规律研究  

Chromatographic Separation and Fragmentation Mechanism in Electrospray Ionization Mass Spectrometry for Colistin B Methanesulfonate

作　　者：刘丹[1,2] 李亮 刘彩 陈笑艳 钟大放 LIU Dan;LI Liang;LIU Cai;CHEN Xiao-yan;ZHONG Da-fang(College of Pharmacy,Nanchang University,Nanchang 330006,China;Center for Drug Metabolism and Pharmacokinetics,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China)

机构地区：[1]南昌大学药学院,江西南昌330006 [2]中国科学院上海药物研究所药物代谢研究中心,上海201203

出　　处：《质谱学报》2018年第6期653-662,共10页Journal of Chinese Mass Spectrometry Society

基　　金：国家自然科学基金(81521005)资助

摘　　要：甲磺酸多黏菌素E_2是多黏菌素E_2的前药,对多药耐药的革兰氏阴性菌引起的感染有效,临床拟用于抗感染治疗。采用超高效液相色谱-四极杆-飞行时间质谱(UPLC-Q-TOF MS)联用技术,电喷雾电离负离子(ESI^-)模式,建立了色谱分离、质谱检测的方法,对不同数目甲磺酸基团取代的多黏菌素E_2进行碰撞诱导解离(CID)研究,推测其质谱裂解规律。结果表明:不同数目甲磺酸基团取代的多黏菌素E_2的准分子离子均为带双电荷的[M-2H]^(2-)离子;对[M-2H]^(2-)离子碰撞裂解,主要为中性丢失CH_2SO_3、H_2SO_3、SO_2、CH_3CHO,未发现酰胺键的断裂。该结果可为进一步研究甲磺酸多黏菌素E_2及结构类似物的质谱裂解规律提供基础,同时也对甲磺酸多黏菌素E的定量分析和药动学研究有参考作用。Colistin is a kind of polypeptide antibiotic,which is used for the treatment of infection caused by gram-negative bacteria.The market colistin is usually the mixture of colistin A and colistin B,and these two components show similar antibiotic activity.However,it was reported that colistin A causes much more damage to kidney than colistin B.In addition,colistin methanesulfonate is inactive prodrug of colistin,which is metabolized to colistin in vivo to kill bacteria.Colistin B methanesulfonate is a safer and more active drug compared with the mixture.There are many researches about colistin and colistin methanesulfonate.However,most of researches for colistin methanesulfonate are indirect.It is necessary to develop a method to directly study colistin B methanesulfonate.In this study,ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF MS)was used to study colistin B methanesulfonate.Acquity UPLC HSS T3 column(100 mm×2.1 mm×1.8μm)and gradient elution were selected for better separation of colistin B with different numbers of methanesulfonic acid groups.The mass detection method for analysis of collision induced dissociation(CID)of colistin B with different numbers of methanesulfonic acid groups and deducing the possible fragmentation pathways was established.It was concluded that the retention time of colistin B with different numbers of methanesulfonic acid groups depended on the number of methanesulfonic acid groups.The more numbers of methanesulfonic acid groups were,the shorter retention time was.In addition,colistin B with different numbers of methanesulfonic acid groups could be separated well through gradient elution but isomers of the same number of methanesulfonic acid groups couldn’t be separated well because of the similar property of these isomers.It was revealed that colistin B with different numbers of methanesulfonic acid groups all had double charge quasi-molecular ion peak[M-2H]^2-.CID research showed that CH2SO3,H2SO3,SO2,CH3CHO were the main ne

关 键 词：超高效液相色谱-电喷雾-四极杆-飞行时间质谱(UPLC-Q-TOF MS) 甲磺酸多黏菌素E2 色谱分离 裂解规律 

分 类 号：O657.63[理学—分析化学]