Methane Elimination upon Collision-Activated Dissociation of Selected Product Ions Formed Upon Gas-Phase Reactions of (Isopropenyloxy)trimethylsilane Facilitates the Mass Spectrometric Classification of Specific Oxygen- and/or Nitrogen-Containing Compounds.

IF 3.1 2区 化学 Q2 BIOCHEMICAL RESEARCH METHODS
Jaskiran Kaur, Kawthar Z Alzarieni, Judy Kuan Yu Liu, Wanru Li, Ruth O Anyaeche, Hilkka I Kenttämaa
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Abstract

Unambiguous identification of drug impurities is of the utmost importance for the pharmaceutical sector. Therefore, access to analytical techniques that enable the reliable characterization of drug impurities during and after the drug development process is required. In this study, tandem mass spectrometry combined with gas-phase ion-molecule reactions followed by collision-activated dissociation (CAD) of specific ion-molecule reaction product ions is demonstrated to enable the identification of nucleophilic compounds with at least one H atom on their nucleophilic atom or a H atom on an adjacent heavy atom. Compounds with different oxygen- and/or nitrogen-containing functionalities and their combinations, such as carboxylic acids, phenols, aldehydes, hydroxylamines, amides, anilines, and sulfonamides, were tested. All analytes were protonated via atmospheric pressure chemical ionization (APCI), transferred into a linear quadrupole ion trap, isolated, and allowed to react with (isopropenyloxy)trimethylsilane (ITS). All protonated compounds studied, including the ones mentioned above as well as many others, react with ITS to form an addition product that has eliminated an acetone molecule. Subjecting these product ions to CAD generated diagnostic fragment ions via the loss of methane for most of the compounds with at least one H atom on their nucleophilic atom or a H atom on an adjacent heavy atom. Only three exceptions were identified. Quantum chemical calculations were employed to delineate the likely mechanisms for the formation of the relevant product ions upon ion-molecule reactions and their fragmentation via elimination of methane.

(异丙烯氧基)三甲基硅烷气相反应形成的选定产物离子碰撞激活解离产生的甲烷消除有助于特定含氧和/或含氮化合物的质谱分类。
药品杂质的明确鉴定对制药行业至关重要。因此,在药物开发过程中和之后,需要获得能够可靠表征药物杂质的分析技术。在本研究中,串联质谱法结合气相离子-分子反应,然后碰撞激活解离(CAD)特定离子-分子反应产物离子,证明能够鉴定亲核化合物,其亲核原子上至少有一个H原子或相邻重原子上有一个H原子。测试了具有不同含氧和/或含氮功能的化合物及其组合,如羧酸、酚类、醛类、羟胺类、酰胺类、苯胺类和磺胺类。所有分析物通过常压化学电离(APCI)质子化,转移到线性四极离子阱中,分离,并与(异丙烯氧基)三甲基硅烷(ITS)反应。所研究的所有质子化化合物,包括上面提到的以及许多其他化合物,都与ITS反应形成一种加成产物,消除了丙酮分子。对大多数亲核原子上至少有一个H原子或相邻重原子上有一个H原子的化合物,将这些产物离子置于CAD中,通过甲烷的损失产生诊断片段离子。只发现了三个例外情况。采用量子化学计算来描述离子-分子反应中相关产物离子的形成及其通过消除甲烷而破碎的可能机制。
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来源期刊
CiteScore
5.50
自引率
9.40%
发文量
257
审稿时长
1 months
期刊介绍: The Journal of the American Society for Mass Spectrometry presents research papers covering all aspects of mass spectrometry, incorporating coverage of fields of scientific inquiry in which mass spectrometry can play a role. Comprehensive in scope, the journal publishes papers on both fundamentals and applications of mass spectrometry. Fundamental subjects include instrumentation principles, design, and demonstration, structures and chemical properties of gas-phase ions, studies of thermodynamic properties, ion spectroscopy, chemical kinetics, mechanisms of ionization, theories of ion fragmentation, cluster ions, and potential energy surfaces. In addition to full papers, the journal offers Communications, Application Notes, and Accounts and Perspectives
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