Journal
ANALYTICAL CHEMISTRY
Volume 93, Issue 2, Pages 964-972Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.analchem.0c03680
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- MRL Future Talent Program
- Agilent Technologies University Relations Program
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Recent advancements in 2D-LC technology have made analyzing complex mixtures more achievable, but the lack of a systematic optimization method remains a challenge. New technologies and computer-assisted modeling approaches are helping to simplify method development and improve the viability of 2D-LC for industrial applications.
Recent developments in two-dimensional liquid chromatography (2D-LC) now make separation and analysis of very complex mixtures achievable. Despite being such a powerful chromatographic tool, current 2D-LC technology requires a series of arduous method development activities poorly suited for a fast-paced industrial environment. Recent introductions of new technologies including active solvent modulation and a support for multicolumn 2D-LC are helping to overcome this stigma. However, many chromatography practitioners believe that the lack of a systematic way to effectively optimize 2D-LC separations is a missing link in securing the viability of 2D-LC as a mainstay for industrial applications. In this work, a computer-assisted modeling approach that dramatically simplifies both offline and online 2D-LC method developments is introduced. Our methodology is based on mapping the separation landscape of pharmaceutically relevant mixtures across both first (D-1) and second (D-2) dimensions using LC Simulator (ACD/Labs) software. Retention models for D-1 and D-2 conditions were built using a minimal number of multifactorial modeling experiments (2 x 2 or 3 x 3 parameters: gradient slope, column temperature, and different column and mobile phase combinations). The approach was first applied to online 2D-LC analysis involving achiral and chiral separations of complex mixtures of enantiomeric species. In these experiments, the retention models proved to be quite accurate for both the D-1 and D-2 separations, with retention time differences between experiments and simulations of less than 3.5%. This software-based concept was also demonstrated for offline 2D-LC purification of drug substances.
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