Temperature-responsive & chiral chromatography for chiral pharmaceuticals (Turaj Rahmani, MDCW 2023)

• 🎤 Presenter: Turaj Rahmani, Adriaan Ampe, Frederic Lynen (Ghent University, Gent, Belgium)

💡 Book in your calendar: 15th Multidimensional Chromatography Workshop (MDCW) January 2024

15th Multidimensional Chromatography (MDC) Workshop 2024

Abstract

Chirality is a prevalent property found in nature, caused by the presence of a (carbon) chiral center in a molecule. Many molecules with different chirality greatly vary in their chemical properties, therefore the ability for separation and detection of these molecules is of utmost importance in the biomedical and pharmaceutical industries.

However, obtaining effective separation of chiral analytes in complex (biological or synthetic) samples requires high resolving power. Which can be theoretically achieved by Comprehensive two-dimensional liquid chromatography (LC x LC), as this technique would allow for a large increase in peak capacity per unit of time. However finding appropriate solvents for the second dimension might be difficult. The slow speed of chiral separations, on the other hand, has hampered the use of chiral stationary phases as the second dimension in 2D-LC.

In this study, the enantioselective separation of a wide range of medicinal substances (log p: 0.9-4.1) is evaluated using a combination of temperature-responsive and reversed-phase chiral liquid chromatography. Temperature-responsive liquid chromatography (TRLC) in the first dimension enables analysis in purely aqueous conditions, allowing for complete (and more general) focusing of organic solutes prior to second-dimension separation. By combining this with small particle (sub-2 micron) based chiral stationary phases as the second dimension in TRLCxChiral-RPLC, a chiral screening platform may be built, which in principle has a lot of potential for tackling chiral screening challenges.