RationaleSecondary‐electrospray ionization (SESI) coupled with high‐resolution mass spectrometry is a powerful tool for the discovery of biomarkers in exhaled breath. A primary electrospray consisting of aqueous formic acid (FA) is currently used to charge the volatile organic compounds in breath. To investigate whether alternate electrospray compositions could enable different metabolite coverage and sensitivities, the electrospray dopants NaI and AgNO3 were tested.MethodsIn a proof‐of‐principle manner, the exhaled breath of one subject was analyzed repeatedly with different electrospray solutions and with the help of a spectral stitching technique. Capillary diameter and position were optimized to achieve proper detection of exhaled breath. The detected features were then compared using formula annotation. Using an evaporation‐based gas standard system, the signal response of the different solutions was probed.ResultsPrincipal component analysis revealed a substantial difference in features detected with AgNO3. With silver, more sulfur‐containing features and more unsaturated hydrocarbon compounds were detected. Furthermore, more primary amines were potentially ionized, as indicated by van Krewelen diagrams. In total, twice as many features were unique to AgNO3 than for other electrospray dopants. Using gas standards at known concentrations, the high sensitivity of FA as a dopant was demonstrated but also indicated alternate sensitivities of the other electrospray solutions.ConclusionsThis work demonstrated the potential of AgNO3 as a complementary dopant for further biomarker discovery in SESI‐based breath analysis.

中文翻译：

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使用二次电喷雾电离高分辨率质谱法用于非靶向呼吸代谢组学的替代电解质溶液

基本原理二次电喷雾电离（SESI）与高分辨率质谱联用是发现呼出气中生物标志物的有力工具。目前使用由甲酸水溶液 (FA) 组成的初级电喷雾来去除呼吸中的挥发性有机化合物。为了研究替代电喷雾组合物是否可以实现不同的代谢物覆盖和灵敏度，电喷雾掺杂剂 NaI 和 AgNO3方法以原理验证的方式，使用不同的电喷雾溶液并借助光谱拼接技术重复分析一名受试者的呼出气体。毛细管直径和位置经过优化，可正确检测呼出气体。然后使用公式注释对检测到的特征进行比较。使用基于蒸发的气体标准系统，探测了不同溶液的信号响应。结果主成分分析表明，AgNO 检测到的特征存在显着差异3。对于银，检测到更多的含硫特征和更多的不饱和烃化合物。此外，如范克鲁伦图所示，更多的伯胺可能被电离。总的来说，AgNO 独有的功能是原来的两倍3与其他电喷雾掺杂剂相比。使用已知浓度的气体标准，证明了 FA 作为掺杂剂的高灵敏度，但也表明了其他电喷雾溶液的替代灵敏度。结论这项工作证明了 AgNO 的潜力3作为补充掺杂剂，用于基于 SESI 的呼吸分析中进一步发现生物标志物。