Separation of Isobaric Lipids in Imaging Mass Spectrometry Using Gas-Phase Charge Inversion Ion/Ion Reactions.
Separation of Isobaric Lipids in Imaging Mass Spectrometry Using Gas-Phase Charge Inversion Ion/Ion Reactions.
复制标题
使用气相电荷反转离子/离子反应在成像质谱中分离同量脂质。
DOI：
10.1021/jasms.3c00081
复制
发表时间：
2023
影响因子：
3.2
通讯作者：
Prentice,BooneM
中科院分区：
文献类型：
--
作者：
Specker,JonathanT;Prentice,BooneM
存在于组织样品中的化学化合物的多样性导致许多同量异位素（即，相同标称质量）的化合物。这些化合物的充分分离和区分是必要的，以确保准确的分析物识别，并避免包括多种化合物的复合图像。在某些情况下，高分辨率精确质量（HRAM）测量能够分辨这些化合物，但HRAM测量并不总是可行的，这取决于仪器平台和所需的实验时间尺度。或者，串联质谱法（MS/MS）可用于进行提高分子特异性的气相转化。虽然常规MS/MS方法采用碰撞诱导解离（CID）来使感兴趣的化合物碎片化，然后分析产物质量，但气相离子/离子反应可用于替代地选择性地与所需类别的分析物反应。在此，我们已经使用气相电荷反转离子/离子反应，选择性地解决磷脂酰胆碱（PC）的等压脂质混合物。1，4-苯二丙酸（PDPA）试剂二价阴离子容易与[M + H]+、[M + Na]+和[M + K]+离子类型反应，以产生每个PC的脱甲基产物阴离子[PC-CH 3]−。这些产物阴离子不再是等压的，现在质量分别相差22 Da（质子化与钠化）和16 Da（钠化与钾化）。该反应已被用于区分大鼠脑组织的成像质谱分析中的同量异序脂质。
The diverse array of chemical compounds present in tissue samples results in many isobaric (i.e., same nominal mass) compounds in imaging mass spectrometry experiments. Adequate separation and differentiation of these compounds is necessary to ensure accurate analyte identification and avoid composite images comprising multiple compounds. High-resolution accurate mass (HRAM) measurements are able to resolve these compounds in some instances, but HRAM measurements are not always feasible depending on the instrument platform and the desired experimental time scale. Alternatively, tandem mass spectrometry (MS/MS) can be used to perform gas-phase transformations that improve molecular specificity. While conventional MS/MS methods employ collision induced dissociation (CID) to fragment compounds of interest and then analyze the product masses, gas-phase ion/ion reactions can be used to instead selectively react with desired classes of analytes. Herein, we have used gas-phase charge inversion ion/ion reactions to selectively resolve phosphatidylcholines (PCs) in isobaric lipid mixtures. A 1,4-phenylenedipropionic acid (PDPA) reagent dianion readily reacts with [M + H]+, [M + Na]+, and [M + K]+ion types to produce demethylated product anions for each PC, [PC – CH3]−. These product anions are no longer isobaric and now differ in mass by 22 Da (protonated versus sodiated) and 16 Da (sodiated versus potassiated), respectively. This reaction has been used to differentiate isobaric lipids in the imaging mass spectrometry analysis of rat brain tissue.