Ion mobility derived collision cross sections to support metabolomics applications.
Ion mobility derived collision cross sections to support metabolomics applications.
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DOI：
10.1021/ac500405x
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发表时间：
2014-04-15
影响因子：
7.4
通讯作者：
Astarita, Giuseppe
中科院分区：
文献类型：
--
作者：
Paglia, Giuseppe;Williams, Jonathan P.;Menikarachchi, Lochana;Thompson, J. Will;Tyldesley-Worster, Richard;Halldorsson, Skarphedinn;Rolfsson, Ottar;Moseley, Arthur;Grant, David;Langridge, James;Palsson, Bernhard O.;Astarita, Giuseppe
代谢组学是生命和健康科学中一种快速发展的分析方法。在代谢组学工作流程中，对感兴趣的代谢物的结构阐明仍然是一个主要的分析挑战。在这里，我们研究使用离子迁移率作为一种工具，以帮助代谢物鉴定。离子迁移率允许测量旋转平均碰撞截面(CCS)，它提供关于气相中分子的离子形状的信息。我们用行波离子迁移率-质谱仪(TW-IM-MS)测定了125种常见代谢物的CCSS。CCS测量在三个独立实验室的仪器上具有很高的重复性(RSD<；5%为99%)。我们还用超高效液相色谱(UPLC)结合TW-IM-MS测定了各种生物基质中CCS的重复性，包括尿液、血浆、血小板和红细胞。对于97%的CCS值，平均RSD为<；2%，而保留时间为80%。最后，作为概念的验证，我们使用UPLC-TW-IM-MS来比较上皮细胞和间充质细胞的细胞代谢体，这是一种用于研究癌症发展的体外模型。实验确定和计算得出的CCS值被用作正交分析参数，与保留时间和准确的质量信息相结合，以确认可能涉及癌症的关键代谢物的身份。因此，我们的结果表明，与传统的分析方法相比，将CCS数据添加到可搜索的数据库和常规代谢组学工作流将增加识别的置信度。
Metabolomics is a rapidly evolving analytical approach in life and health sciences. The structural elucidation of the metabolites of interest remains a major analytical challenge in the metabolomics workflow. Here, we investigate the use of ion mobility as a tool to aid metabolite identification. Ion mobility allows for the measurement of the rotationally averaged collision cross-section (CCS), which gives information about the ionic shape of a molecule in the gas phase. We measured the CCSs of 125 common metabolites using traveling-wave ion mobility-mass spectrometry (TW-IM-MS). CCS measurements were highly reproducible on instruments located in three independent laboratories (RSD < 5% for 99%). We also determined the reproducibility of CCS measurements in various biological matrixes including urine, plasma, platelets, and red blood cells using ultra performance liquid chromatography (UPLC) coupled with TW-IM-MS. The mean RSD was < 2% for 97% of the CCS values, compared to 80% of retention times. Finally, as proof of concept, we used UPLC–TW-IM-MS to compare the cellular metabolome of epithelial and mesenchymal cells, an in vitro model used to study cancer development. Experimentally determined and computationally derived CCS values were used as orthogonal analytical parameters in combination with retention time and accurate mass information to confirm the identity of key metabolites potentially involved in cancer. Thus, our results indicate that adding CCS data to searchable databases and to routine metabolomics workflows will increase the identification confidence compared to traditional analytical approaches.
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影响因子：
7.4
作者：
Kaplan, Kimberly;Dwivedi, Prabha;Hill, Herbert H., Jr.
通讯作者：
Hill, Herbert H., Jr.
影响因子：
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Bond, Nicholas J.;Shliaha, Pavel V.;Gatto, Laurent
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影响因子：
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作者：
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通讯作者：
Eberlin, Marcos N.
影响因子：
1.8
作者：
Dwivedi P;Schultz AJ;Hill HH
通讯作者：
Hill HH
影响因子：
7.4
作者：
Campuzano, Iain;Bush, Matthew F.;Kim, Hugh I.
通讯作者：
Kim, Hugh I.