Ouyang Dan, Zheng Qiong, Huang Huan, Cai Zongwei, Lin Zian
Ministry of Education Key Laboratory of Analytical Science for Food Safety and Biology, Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety, College of Chemistry, Fuzhou University, Fuzhou, Fujian 350108, China.
State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, 224 Waterloo Road, Kowloon Tong, Hong Kong.
Anal Chem. 2021 Nov 30;93(47):15573-15578. doi: 10.1021/acs.analchem.1c01743. Epub 2021 Nov 16.
Although matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has become a ubiquitous and effective tool for macromolecules, direct analysis of small molecules by MALDI-MS using conventional organic matrices poses a challenge. Herein, a large-area, uniform, and stable covalent organic framework (COF) nanofilm prepared directly on indium-tin oxide (ITO) glass was first introduced as a substrate for LDI-MS, which showed enhanced sensitivity, no background interference, and high reproducibility in the analysis of diverse small molecules. Taking into account all these merits, an attractive approach of COF nanofilm-based LDI-MS was developed to quantitatively evaluate the pharmacokinetics of 5-fluorouracil (5-FU) in mouse plasma. A good linear relationship (10-20,000 ng/mL) and a low limit of detection (LOD) for 5-FU (∼100 pg/mL) were achieved. In view of the fact that the COF nanofilm was uniform and without the requirement of additional matrix spraying, it was further extended for LDI-MS imaging (LDI-MSI) to visualize the spatial distribution of 5-FU in mouse liver at different interval times after intravenous and intragastric administrations. The results indicated that the decay of 5-FU in mouse liver obtained with the COF nanofilm-based LDI-MSI was consistent with the tendency of 5-FU pharmacokinetics. This work not only offers an alternative solution for LDI-MS/MSI analysis of small molecules but also extends the application fields of COF nanofilm in MS research.
尽管基质辅助激光解吸/电离质谱（MALDI-MS）已成为分析大分子的常用且有效的工具，但使用传统有机基质通过MALDI-MS直接分析小分子却面临挑战。在此，首次引入了一种直接在氧化铟锡（ITO）玻璃上制备的大面积、均匀且稳定的共价有机框架（COF）纳米薄膜作为激光解吸电离质谱（LDI-MS）的基质，该基质在分析多种小分子时表现出增强的灵敏度、无背景干扰以及高重现性。考虑到所有这些优点，开发了一种基于COF纳米薄膜的LDI-MS的有吸引力的方法，用于定量评估小鼠血浆中5-氟尿嘧啶（5-FU）的药代动力学。实现了5-FU良好的线性关系（10 - 20,000 ng/mL）和低检测限（LOD）（约100 pg/mL）。鉴于COF纳米薄膜均匀且无需额外喷雾基质，它进一步扩展用于LDI-MS成像（LDI-MSI），以可视化静脉注射和灌胃给药后不同时间间隔小鼠肝脏中5-FU的空间分布。结果表明，基于COF纳米薄膜的LDI-MSI获得的小鼠肝脏中5-FU的衰减与5-FU药代动力学趋势一致。这项工作不仅为小分子的LDI-MS/MSI分析提供了一种替代解决方案，还扩展了COF纳米薄膜在质谱研究中的应用领域。
