Polarity-Tuning Derivatization-LC-MS Approach for Probing Global Carboxyl-Containing Metabolites in Colorectal Cancer
| Autor: | Guoxin Huang, Na Li, Binbin Tan, Jian-Lin Wu, W.L. Wendy Hsiao, Xiqing Bian, Liang Liu, Mingquan Guo, Li Fu, Bao-qing Sun |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
chemistry.chemical_classification Chromatography Structural similarity Polarity (physics) 010401 analytical chemistry Structural diversity Mass spectrometry 01 natural sciences Mass Spectrometry 0104 chemical sciences Analytical Chemistry Amino acid Citric acid cycle 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology chemistry Liquid chromatography–mass spectrometry Humans Metabolomics Amines Colorectal Neoplasms Derivatization Chromatography High Pressure Liquid |
| Zdroj: | Analytical Chemistry. 90:11210-11215 |
| ISSN: | 1520-6882 0003-2700 |
| DOI: | 10.1021/acs.analchem.8b01873 |
| Popis: | Carboxyl-containing metabolites (CCMs) widely exist in living systems and are the essential components for life. Global characteristics of CCMs in biological samples are critical for the understanding of physiological processes and the discovery for the onset of relevant diseases. However, their determination represents a challenge due to enormous polarity differences, structural diversity, high structural similarity, and poor ionization efficiency in mass spectrometry. Herein, 5-(diisopropylamino)amylamine (DIAAA) derivatization coupled with liquid chromatography-mass spectrometry (LC-MS) was developed for mapping the CCMs. With this methodology, the sensitivity was significantly enhanced. More importantly, the hydrophobicity of polar CCMs, amino acids, TCA cycle intermediates, and short-chain fatty acids and the hydrophilicity of low-polar CCMs, long-chain fatty acids, and bile acids were significantly increased, resulting in a remarkable separation efficiency for which 68 CCMs can be simultaneously determined. Furthermore, the polarity-tuning effect was confirmed to be induced by the different impacts of aliphatic chains and nitrogen atom in DIAAA, the latter existing as a cation in the acidic mobile phase, using different derivatization reagents. Finally, this derivatization method was utilized to hunt for the potential biomarkers in colorectal cancer (CRC) patients and 52 CCMs, related with several key metabolic pathways, including amino acids metabolism, TCA cycle, fatty acid metabolism, pyruvate metabolism, and gut flora metabolism were identified. This innovative polarity-tuning derivatization-LC-MS approach was proved to be a valuable tool for probing global metabolome with high separation efficiency and sensitivity in various biological samples. |
| Databáze: | OpenAIRE |
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