Reaction monitoring of aliphatic amines in supercritical carbon dioxide by proton nuclear magnetic resonance spectroscopy and implications for supercritical fluid chromatography.

In the recent years, it has repeatedly been stated that amines react with CO2 and can therefore not be chromatographed under supercritical conditions with CO2. The aim of the present work is to elucidate the structural requirements and conditions that can lead to the reaction of an amine analyte with CO2 and, if this occurs, the structure of the formed product. The use of on-line nuclear magnetic resonance (NMR) spectroscopy with a flow probe for supercritical fluid chromatography (SFC) enables the investigation of these unstable analytes in supercritical mediums.

Preparative resolution of drug racemates to study the chiroptical properties of their enantiomers.

The present work is focused on the resolution of ten racemates, in order to study their chiroptical properties and to test the validity of the requirement specified in the European Pharmacopeia (EP) for demonstrating that a drug entity is a racemate. This work shows that the optical purity of enantiomers and non racemic mixtures of a number of compounds can be determined more accurately by circular dichroic (CD) spectroscopy than by a measurement of the angle of rotation (AoR), the EP requirement. Using only the AoR, some of the racemates could not be distinguished from the enantiomers.

Direct separation of captopril diastereoisomers including their rotational isomers by RP-LC using a teicoplanin column.

A direct reversed-phase liquid chromatography (LC) method has been developed for the separation and analysis of captopril and its 2R,2S diastereoisomer using a teicoplanin stationary phase. The proline containing diastereoisomers, which are known to form conformers in aqueous solution, were also separated from their rotational isomers. The influence of temperature, different organic modifiers and buffer type, concentration and pH were optimised to obtain a working resolution between the two diastereoisomers and their respective rotational isomers.

Polar organic phase liquid chromatography with packed capillary columns using a vancomycin chiral stationary phase.

Vancomycin immobilized on silica served as the chiral stationary phase (CSP) in this investigation with polar organic solvents as the mobile phase in liquid chromatography (LC). It was shown that trace amounts of water were beneficial for improving peak shape and efficiency. To regulate the retention and selectivity an acid and/or base were added to the mobile phase where an excess of acid was shown to be preferential for enantioseparation.

Packed-column supercritical fluid chromatography for the purity analysis of clevidipine, a new dihydropyridine drug.

In this paper we describe a packed column supercritical fluid chromatography method that can be used for the analysis of a new dihydropyridine substance. The method is based on methanol-modified carbon dioxide as the mobile phase and Hypersil bare silica as column support at a column temperature of 50 degrees C and 150 bar as back pressure. Using an adjusted methanol gradient the most likely by-products can be separated and detected (240 nm) within 13 min.