Functionalization using polymer or silane? A practical test method to characterize hydrophilic interaction chromatography phases in terms of their functionalization method.

Herein, commercially available columns employed in hydrophilic interaction chromatography (HILIC) were characterized by determining their ability to selectively distinguish the minute structural differences between small molecules such as nucleosides and xanthines in complex sample matrices. Principal component analysis (PCA) was applied to the data obtained from structurally similar analytes, and the results showed that HILIC columns could generally be classified into two groups: (i) silane-modified columns that were prepared from either native silica particles or silica particles modified with low-molecular-weight silanes and (ii) polymer-modified columns obtained from silica particles functionalized with organic polymers. These two groups could be further subdivided based on the functionalities attached to the respective stationary phases.

Tetrahydro-naphthols as orally available TRPV1 inhibitors.

Starting from a naphthol-based lead series with low oral bioavailability, we have identified potent TRPV1 antagonists with oral bioavailability in rats. These compounds emerged from SAR studies aimed at replacing the lead's phenol structure whilst maintaining potency. Compound rac-6a is an orally available TRPV1 antagonist with single-digit nanomolar activity.

Chromatographic characterization of hydrophilic interaction liquid chromatography stationary phases: hydrophilicity, charge effects, structural selectivity, and separation efficiency.

Fourteen commercially available particle-packed columns and a monolithic column for hydrophilic interaction liquid chromatography (HILIC) were characterized in terms of the degree of hydrophilicity, the selectivity for hydrophilic-hydrophobic substituents, the selectivity for the regio and configurational differences in hydrophilic substituents, the selectivity for molecular shapes, the evaluation of electrostatic interactions, and the evaluation of the acidic-basic nature of the stationary phases using nucleoside derivatives, phenyl glucoside derivatives, xanthine derivatives, sodium p-toluenesulfonate, and trimethylphenylammonium chloride as a set of samples. Principal component analysis based on the data of retention factors could separate three clusters of the HILIC phases. The column efficiency and the peak asymmetry factors were also discussed.