Baseline separation and analysis of multicomponent mixtures of closely related pharmaceuticals using single column selectivity can often be challenging, requiring the combination of orthogonal stationary and mobile phase methods to monitor all the species and optimize reaction outcomes. In recent years, two-dimensional liquid chromatography (2D-LC) has become a valuable tool for improving peak capacity and selectivity. Though powerful, standard 2D-LC instrumentation and software can often lead to tedious method development and has a requirement for very specific expertise that is poorly suited for a fast-paced industrial environment. In this regard, the introduction of an automated online 2D-LC setup that could screen multiple columns in both dimensions without manual intervention will undeniably serve to streamline column/mobile phase selection and secure the viability of 2D-LC as a mainstay instrument for industrial applications. Herein, we introduce and investigate a multicolumn online 2D-LC approach that simplifies column screening and method development dramatically. This setup incorporates 6-position column selection valve technology whose functionality enables us to combine multiple columns in the first and second dimensions. This strategy in conjunction with diode array detection (DAD) in both dimensions and mass spectrometry (MS) acquisition in the second dimension serves to explore different columns and mobile phases as a framework for screening targeted compounds in multicomponent mixtures without having to perform chromatographic purification. Multiple online heart cutting achiral RPLC - achiral RPLC and achiral RPLC - chiral RPLC coupled to DAD and ESI-MS methods combining several stationary phase selectivity in an automated fashion are successfully applied to the separation and analysis of complex mixtures of drug substances, where in many instances, traditional 1D-ultra-high performance liquid chromatography (UHPLC) fails or delivers sub-optimal results. This automated online multicolumn 2D-LC workflow enables rapid and efficient identification of column/eluent combinations, as well as sample analysis across multiple columns in both dimensions overnight with a single click.

中文翻译：

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引入在线多柱二维液相色谱筛查技术，可轻松选择二维和固定相条件。

使用单色谱柱选择性对密切相关的药物的多组分混合物进行基线分离和分析通常具有挑战性，需要结合正交固定相和流动相方法来监测所有种类并优化反应结果。近年来，二维液相色谱（2D-LC）已成为提高峰容量和选择性的有价值的工具。尽管功能强大，但是标准的2D-LC仪器和软件通常会导致乏味的方法开发，并且需要非常特殊的专业知识，而这些专业知识不适合快节奏的工业环境。在这方面，引入自动化的在线2D-LC设置可以在不进行人工干预的情况下在两个维度上筛选多根色谱柱，无疑将有助于简化色谱柱/流动相的选择，并确保2D-LC作为工业应用的主要手段的可行性。本文中，我们介绍并研究了一种多柱在线二维液相色谱方法，该方法可大大简化色谱柱筛选和方法开发。该设置采用了6位柱选择阀技术，其功能使我们能够在第一维和第二维上组合多个色谱柱。此策略与二维空间中的二极管阵列检测（DAD）和二维空间中的质谱（MS）采集相结合，可探索不同的色谱柱和流动相，以此作为筛选多组分混合物中目标化合物的框架，而无需进行色谱纯化。多种在线心脏切割非手性RPLC-非手性RPLC和非手性RPLC-手性RPLC结合DAD和ESI-MS方法，以自动化方式结合了几种固定相选择性，已成功地用于分离和分析药物的复杂混合物，其中许多例如，传统的一维超高效液相色谱（UHPLC）失败或无法达到最佳效果。