High-Resolution Elemental Mass Spectrometry Using LC-ICP-Nanospray-Orbitrap for Simultaneous and Species-Independent Quantitation of Fluorinated and Chlorinated Compounds.
High-Resolution Elemental Mass Spectrometry Using LC-ICP-Nanospray-Orbitrap for Simultaneous and Species-Independent Quantitation of Fluorinated and Chlorinated Compounds.
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DOI：
10.1021/acs.analchem.2c02359
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发表时间：
2022-08-30
影响因子：
7.4
通讯作者：
Jorabchi, Kaveh
中科院分区：
文献类型：
--
作者：
Redeker, Frenio A.;Lesniewski, Joseph E.;Hahm, Grace;McMahon, William P.;Jorabchi, Kaveh
氟和氯的同时元素检测提供了氟化和氯化化合物及其转化产物的定量，而不需要特定于化合物的标准。尽管应用广泛，但目前的电感耦合等离子体(ICP)-MS方法在离子形成和消除同压干扰方面的基本和技术缺陷阻碍了这一能力的实现。这些障碍在这里通过化学电离方法得到缓解。分析物中的氟和氯首先通过等离子体后复合被电感耦合等离子体转化为氢氟酸和氯化氢，然后与纳米射线提供的含钡离子反应，生成BaF+和BaCl+作为元素报告离子。值得注意的是，该方法很容易与Orbitrap MS对接，它可以在分辨率低至35000的情况下消除等压干扰，远高于目前的电感耦合等离子体质谱仪。此外，该仪器很容易恢复到ESI-MS模式，以进行互补的分子表征。为了展示分析能力，采用与物种无关的校正方法开发了反相液相色谱分离化合物的快速定量工作流程。氟和氯的独立测量结果相互吻合，在柱上提供了~gt；90%的回收率和8-12pmolCl和5-12pmolF的精密度。然后将该工作流程与同一仪器上的LC-ESI-MS一起应用于体外药物代谢物的鉴定和定量，得到药物相关物质的总回收率为80%，次要代谢物的定量总和为药物相关化合物的8%。这些结果突出了氟和氯同时存在的优势，可用于快速定量，并在早期药物开发中应用。
Simultaneous elemental detection of F and Cl offers quantitation of fluorinated and chlorinated compounds and their transformation products without compound-specific standards. Despite wide-ranging applications, this capability has been hindered by fundamental and technical shortcomings of current inductively coupled plasma (ICP)-MS methods in ion formation and isobaric interference elimination. These hurdles are alleviated here via a chemical ionization method. Fluorine and chlorine in analytes are first converted to HF and HCl by an ICP with post-plasma recombination, and subsequently react with barium-containing ions supplied by a nanospray, yielding BaF+ and BaCl+ as elemental reporter ions. Notably, the method is readily interfaced to an Orbitrap MS which eliminates isobaric interferences at resolving powers as low as 35000, far greater than that of current ICP-MS instruments. Moreover, the instrument is easily reverted to ESI-MS mode for complementary molecular characterization. To demonstrate analytical capabilities, a workflow for rapid quantitation of compounds separated by reversed-phase liquid chromatography is developed using a species-independent calibration. The independent F and Cl measurements agree with each other, providing recoveries of >90% and LODs of 8–12 pmol Cl and 5–12 pmol F on column. The workflow along with LC-ESI-MS on the same instrument are then applied to identify and quantify in-vitro drug metabolites, yielding total drug related material recoveries of >80% and quantitation of minor metabolites summing to 8% of the total drug-related compounds. These results highlight the strengths of simultaneous F and Cl speciation for rapid quantitation with applications in early drug development.
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影响因子：
6.2
作者：
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通讯作者：
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通讯作者：
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