Alongside the success of protein-based bio-therapeutics over the last decades and facilitated by advances both in protein engineering and manufacturing, new product formats progressively enter into the biopharmaceutical industry's pipelines with major implications on the analytical methods used for their characterization. While conventional approaches have proved sufficient for standard (IgG-like) molecules, the increased complexity of novel formats requires proper adjustments of the employed methodologies, in particular with regard to separation-based techniques coupled to UV/FLD detection. After introducing the status quo for the characterization of biopharmaceuticals in quality control settings, this review provides a comprehensive portrayal of emerging LC-MS based technologies, which have already demonstrated their potential to complement the existing analytical toolbox. In this context, the benefits of native LC-MS and two-/multidimensional LC-MS applications to assess product attributes while preserving the higher-order structure are discussed based on challenges arising from the analysis of complex product formats.

中文翻译：

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基于LC-MS的基于蛋白质的生物治疗剂表征的最新进展-应对格式复杂性不断提高带来的分析挑战。

在过去的几十年中，基于蛋白质的生物疗法取得了成功，并且在蛋白质工程和制造方面取得了进步，新产品形式逐渐进入生物制药行业，对表征其分析方法产生了重大影响。尽管传统方法已被证明足以用于标准（IgG样）分子，但新形式复杂性的提高要求对所采用的方法进行适当调整，尤其是在与UV / FLD检测耦合的基于分离的技术方面。在介绍了质量控制环境中表征生物制药的现状之后，本综述全面介绍了新兴的基于LC-MS的技术，已经证明了它们有潜力补充现有的分析工具箱。在这种情况下，基于对复杂产品格式的分析所带来的挑战，讨论了本机LC-MS和二维/多维LC-MS应用程序在评估产品属性同时保留高阶结构的优势。