Multiple ionization mass spectrometry strategy used to reveal the complexity of metabolomics
Multiple ionization mass spectrometry strategy used to reveal the complexity of metabolomics
复制标题
DOI：
10.1021/ac701982e
复制
发表时间：
2008-01-15
影响因子：
7.4
通讯作者：
Siuzdak, Gary
中科院分区：
文献类型：
--
作者：
Nordstrom, Anders;Want, Elizabeth;Siuzdak, Gary
基于对人血清提取液的分析，提出了一种多电离质谱分析方法。在正(+)和负(-)两种电离模式下，色层分离与大气压电喷雾电离(ESI)和大气压化学电离(APCI)相结合。此外，还将表面基质辅助激光解吸电离(MALDI)和硅解吸电离(DIOS)质谱学技术与馏分收集分离和离线质谱学相结合。使用XCMS软件对原始数据进行处理产生了时间对准的离子特征，该特征被定义为在唯一的保留时间处的唯一的m/z。比较了在两种电离模式下，采用ESI和APCI接口的LC-MS获得的离子特征列表，并生成了唯一的离子表。非冗余、独特的离子特征被定义为在相同的保留时间内，在其他电离方法中没有观察到与[M+H](+)、[M-H](-)或[M+Na](+)相对应的质量数。使用ESI对提取的血清进行(+)和(-)离子分析，结果在(-)ESI模式中检测到90%的额外独特离子。用APCI补充ESI分析导致独特离子的额外类似20%的增加。最后，将ESI/APCI电离与馏分收集、离线MALDI和DIOS质谱学相结合。将LC-MS中采集的与收集的组分对应的数据中的部分总离子流色谱图相加，并编制m/z表，并与从Dios/MALDI谱获得的m/z表进行比较。观察到，对于每个组分，Dios占检测到的独特离子的50%左右。这些结果表明，真正的全球代谢组学将需要多种电离技术来解决固有的代谢物多样性，从而解决代谢组学研究的复杂性。
A multiple ionization mass spectrometry strategy is presented based on the analysis of human serum extracts. Chromatographic separation was interfaced inline with the atmospheric pressure ionization techniques electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) in both positive (+) and negative (-) ionization modes. Furthermore, surface-based matrix-assisted laser desorption/ionization (MALDI) and desorption ionization on silicon (DIOS) mass spectrometry were also integrated with the separation through fraction collection and offline mass spectrometry. Processing of raw data using the XCMS software resulted in time-aligned ion features, which are defined as a unique m/z at a unique retention time. The ion feature lists obtained through LC-MS with ESI and APCI interfaces in both ionization modes were compared, and unique ion tables were generated. Nonredundant, unique ion features, were defined as mass numbers for which no mass numbers corresponding to [M + H](+), [M - H](-), or [M + Na](+) were observed in the other ionization methods at the same retention time. Analysis of the extracted serum using ESI for both (+) and (-) ions resulted in > 90% additional unique ions being detected in the (-) ESI mode. Complementing the ESI analysis with APCI resulted in an additional similar to 20% increase in unique ions. Finally, ESI/APCI ionization was combined with fraction collection and offline-MALDI and DIOS mass spectrometry. The parts of the total ion current chromatograms in the LC-MS acquired data corresponding to collected fractions were summed, and m/z lists were compiled and compared to the m/z lists obtained from the DIOS/MALDI spectra. It was observed that, for each fraction, DIOS accounted for similar to 50% of the unique ions detected. These results suggest that true global metabolomics will require multiple ionization technologies to address the inherent metabolite diversity and therefore the complexity in and of metabolomics studies.