Next Generation Elemental Mass Spectrometry of Non-Metals

项目总结 液-质联用(LC-MS)已成为生物医学中一项有影响力的技术 调查。然而，使用这种方法对化合物的绝对量化仍然是一个重大挑战。 技术。在分子LC-MS中，每种化合物都需要一个分析标准来进行绝对 浓度测量。对于许多已鉴定的化合物，标准往往是不可用的， 需要很大的努力来合成和提纯以用于分析目的。标准问题 在异种代谢的定量描述中经常遇到不可用现象，例如 药物开发。该提案涉及在没有化合物特定标准的情况下通过以下方式进行量化 F、Cl、P和S的元素质谱学进展--大小生物中普遍存在的杂原子 重要的分子。元素质谱仪提供了不依赖化合物的LC中元素的定量。 分离的化合物。元素浓度随后很容易转化为分子。 使用分子式(由分子LC-MS确认)的浓度。在这项拟议的研究中， 与元素质谱仪相比，元素质谱仪对杂原子的分析性能显著提高 现有的基本MS技术。这种改进源于发展一种元素电离 该方法提供：1)F和Cl的有效电离的新机制，以及2)与 分子LC-MS平台中先进的离子分离方法，能够减少同量异压 通过超高分辨率MS和离子迁移率分离产生的干扰以前在 值得注意的是，第二个优点也促进了元素定量在 通过消除对专用基本MS平台的需求，进行生物医学研究。我们的 调查将与仪器制造和制药合作伙伴合作 来自行业，突出了拟议技术的影响和可采纳性。

Project summary Liquid chromatography-mass spectrometry (LC-MS) has become an influential technology in biomedical investigations. However, absolute quantification of compounds remains a major challenge using this technique. In molecular LC-MS, an analytical standard for each compound is needed for absolute concentration measurements. The standards are often unavailable for many identified compounds, requiring major efforts for their synthesis and purification for analytical purposes. The problem of standard unavailability is frequently encountered in quantitative characterization of xenobiotic metabolism, e.g. in drug development. This proposal addresses quantification without compound-specific standards by advancing elemental MS of F, Cl, P, and S, prevalent heteroatoms in both small and large biologically important molecules. Elemental MS provides compound-independent quantification of elements in LC- separated compounds. The elemental concentrations are then readily translated to molecular concentrations using molecular formulae (confirmed by molecular LC-MS). In the proposed research, analytical performance of elemental MS for heteroatoms is significantly enhanced compared to the existing elemental MS technologies. The improvements arise from developing an elemental ionization method that offers: 1) a new mechanism for efficient ionization of F and Cl, and 2) compatibility with advanced ion separation methods in molecular LC-MS platforms, enabling reduction of isobaric interferences via ultra-high-resolution MS and ion mobility separations previously unavailable in elemental MS. Notably, the second advantage also facilitates adoption of elemental quantification in biomedical investigations by eliminating the need for a dedicated elemental MS platform. Our investigations will be in collaboration with instrument manufacturing and pharmaceutical collaborators from industry, highlighting the impact and adoptability of the proposed technique.