Less Configuration and More Dimensionality: Preparative Heart-Cut Multidimensional Liquid Chromatography Based on Trapping Arrays

Abstract

The resolving power of multiple dimensional liquid chromatography (mD-LC) is multiplicative as it adds dimensions. However, the issue in creating a preparative mD-LC system is that the higher the dimensionality, the more complicated the system configuration. Thus, we presented a new configuration of preparative mD-LC using one set of LC modules and trapping array-based multiple heart-cut interfaces. A preparative two-dimensional liquid chromatography (2D-LC) separation of herbal medicine formulation produced 40 compounds with a purity of >90%. During the separation process, the interface stores the fractions and allocates positions for the fractions from a different dimension; LC draws the fraction from the interface, makes nD separation, and sends isolated fractions to the interface. By repeating this process, we achieved variable dimensionality of LC separations. We also presented a preparative 3D-LC separation of herbal medicines to validate the principle of “less configuration and more dimensionality”. Thus, we can explore the higher dimensional preparative separations. The developed preparative mD-LC displayed exceptional power in the isolation of various compounds and has great potential in the application of natural products.

High-Throughput Purification in Drug Discovery: Scaling New Heights of Productivity

“…Advances in automated liquid–liquid extractions, , including microdroplets, and solid phase extraction (SPE)/​resin cleanup methods offer potentially faster and cheaper alternativesbut they cannot match the generic capabilities of C18 HPLC, with a wide compound structure range and high purity levels. Sample preparation, using SPE, for crude samples and advanced techniques of “trap and release” of “heart-cut” samples, combined with LCMS, offer the ultimate purification solution.…”