Over the past several years, hyphenation of native (nondenaturing) liquid chromatography (nLC) methods, such as size exclusion chromatography (SEC), ion exchange chromatography (IEX), and hydrophobic interaction chromatography (HIC) with mass spectrometry (MS) have become increasingly popular to study the size, charge, and structural heterogeneity of protein drug products. Despite the availability of a wide variety of nLC-MS methods, an integrated platform that can accommodate different applications is still lacking. In this study, we described the development of a versatile, sensitive, and robust nLC-MS platform that can support various nLC-MS applications. In particular, the developed platform can tolerate a wide range of LC flow rates and high salt concentrations, which are critical for accommodating different nLC methods. In addition, a dopant-modified desolvation gas can be readily applied on this platform to achieve online charge-reduction native MS, which improves the characterization of both heterogeneous and labile biomolecules. Finally, we demonstrated that this nLC-MS platform is highly sensitive and robust and can be routinely applied in protein drug characterization.

中文翻译：

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用于蛋白质药物完整质量分析的多功能、灵敏且稳健的天然 LC-MS 平台。

在过去几年中，天然（非变性）液相色谱 (nLC) 方法的连字符，例如尺寸排阻色谱 (SEC)、离子交换色谱 (IEX) 和疏水相互作用色谱 (HIC) 与质谱 (MS) 已成为研究蛋白质药物产品的大小、电荷和结构异质性越来越受欢迎。尽管有多种 nLC-MS 方法可用，但仍然缺乏可以适应不同应用的集成平台。在本研究中，我们描述了一种多功能、灵敏且稳健的 nLC-MS 平台的开发，该平台可以支持各种 nLC-MS 应用。特别是，开发的平台可以承受范围广泛的 LC 流速和高盐浓度，这对于适应不同的 nLC 方法至关重要。此外，掺杂剂改性的去溶剂化气体可以很容易地应用于该平台，以实现在线电荷减少原生 MS，从而改善异质和不稳定生物分子的表征。最后，我们证明了该 nLC-MS 平台高度灵敏且稳健，可常规应用于蛋白质药物表征。