Potential of adsorption isotherm measurements for closer elucidating of binding in chiral liquid chromatographic phase systems

Abstract

The human body is a chiral environment and many drugs are chiral and interact differently depending on the type of enantiomer. Therefore, the interest in analytical and preparative separations of enantiomers has steadily increased over the years. LC is today the most important technique in analytical laboratories worldwide. The key to understand the separation system lies in the adsorption isotherm, which describes the equilibrium distribution of solutes between the mobile and stationary phases. By measuring adsorption isotherms in chiral phase systems, a deeper interpenetration concerning enantioselective and non-selective binding energies and adsorption processes is possible. Furthermore, this data provides the core information needed to optimize preparative chromatographic processes for purification of single enantiomers. However, the measurement of adsorption isotherms is a delicate matter and there are many dangerous pitfalls that may produce erroneous results and even wrong mechanistic conclusions. This review summarizes the most relevant methods and a workflow will be given for avoiding the common pitfalls and obtaining reliable data. Several applications from the literature are also treated to give insight in what information can potentially be obtained from using this methodology.

Characterization of warfarin unusual peak profiles on oligoproline chiral high performance liquid chromatography columns

“…Later, a numerical investigation ascertained the most favorable band-shape composition in preparative chromatography for a particular enantiomer [70]. These previous studies demonstrated adsorbing additives, in particular strongly bound, can have extreme impact on retention times and peak shapes [71,72]. We have previously prepared and evaluated two novel oligoproline CSPs (Fig.…”

Determination of adsorption isotherms in supercritical fluid chromatography

“…To transfer dynamic LC adsorption isotherm acquisition methods [4,5,37] to SFC one must ensure that the column is operated at constant volumetric flow rate under isopycnic and isothermal conditions. Furthermore, it is also necessary to have accurate measurements of the actual mass flow, pressure and temperature in order for SFC experiments to be reproducible.…”

“…To accurately determine adsorption isotherms using dynamic methods, as we do in this study, it is important to know the volumetric flow of the mobile phase in the column [4,5,9,37]. To calculate the volumetric flow, see Eq.…”

A modified coupled complex boundary method for an inverse chromatography problem

“…The outcome of a chromatographic separation is strongly dependent on the adsorption isotherms of the solutes, since they dictate the separation factors and saturation capacities, i.e., how much solute can be adsorbed. Therefore, estimation of adsorption isotherms is crucial and also gives deeper understanding of the separation processes [3,4,9,12,14,31].…”