Next Generation Elemental Mass Spectrometry of Non-Metals

项目摘要 液相色谱-质谱联用技术（LC-MS）已成为生物医学领域的一项重要技术 调查事务所然而，化合物的绝对定量仍然是使用该方法的主要挑战。 法在分子LC-MS中，需要每种化合物的分析标准品以确定绝对浓度。 浓度测量。对于许多已鉴定的化合物，标准品往往是不可用的， 为了分析目的，需要对其进行大量的合成和纯化。标准问题 在定量表征异生物质代谢中经常遇到不可用性，例如， 药物开发该提案通过以下方式解决了在没有化合物特定标准品的情况下的定量问题： 先进的元素MS的F，Cl，P和S，普遍杂原子在小和大的生物 重要分子元素MS提供LC中元素的化合物独立定量。 分离的化合物。元素浓度然后很容易地转化为分子 使用分子式测定浓度（通过分子LC-MS确认）。在拟议的研究中， 元素MS对杂原子的分析性能显著增强， 现有的MS技术。这些改进来自于开发一种元素电离 方法提供：1）一种新的机制，有效电离的F和Cl，和2）兼容性 在分子LC-MS平台中采用先进的离子分离方法， 通过超高分辨率MS和离子迁移率分离的干扰， 值得注意的是，第二个优点也有利于在质谱中采用元素定量。 通过消除对专用元素MS平台的需要，可用于生物医学研究。我们 调查将与仪器制造和制药合作者合作 从工业，突出的影响和所提出的技术的可采用性。

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.