Coupled Achiral/Chiral Column Techniques in Subcritical Fluid Chromatography for the Separation of Chiral and Nonchiral Compounds

Abstract

A multicolumn approach was developed to address the limited achiral selectivity of chiral stationary phases. Groups of structurally related compounds, including beta-blockers and 1,4-benzodiazepines, were separated using coupled achiral/chiral stationary phases under subcritical fluid conditions. The achiral selectivity of amino and cyano stationary phases was used to modify the resolution of compounds on a Chiralcel OD chiral stationary phase by combining the achiral and chiral columns in series. In the case of the benzodiazepines, separation of achiral compounds was performed concurrently with the enantioseparation of chiral molecules. The separation of components of a multidrug cough and cold medication was also demonstrated on a cyano column coupled with a Chiralpak AD chiral stationary phase. The use of modified carbon dioxide eluents eliminated the mobile phase incompatibility problems associated with column coupling in liquid chromatography and incorporated the high efficiency of sub- and supercritical fluid chromatography.

Supercritical Fluid Chromatography

“…Different types of columns can be coupled to provide additional selectivity, or multiple columns of the same type can be connected in series to increase column length and thereby increase resolution. Coupling of achiral and chiral columns was reported to address the limited achiral selectivity of chiral stationary phases (Phinney et al, 1998 ). Serial connection of fi ve 25 -cmlong cyanopropyl columns generated ∼ 100,000 plates and enabled the separation of analytes that coeluted on a liquid.…”

“…Coupling of achiral/chiral columns was reported to address the limited achiral selectivity of chiral stationary phases. An amino or cyano column was coupled in series with a Chiralcel OD column to adjust the selectivity (Phinney et al, 1998 ). Separations of both achiral and chiral components were demonstrated for β -blockers, benzodiazepines, as well as for a multidrug medication.…”

Separation of Chiral Compounds on Polysaccharide Columns

“…Phinney et al coupled achiral columns together with Chiralcel OD or Chiralpak AD columns in SFC mode to separate complex mixtures containing one or more pairs of enantiomers [217]. Barnhart et al coupled Chiralpak AD-H and Chiralcel OD-H columns together in SFC mode to separate a mixture of four stereoisomers that could not be separated on either column alone [218].…”

Solving multicomponent chiral separation challenges using a new SFC tandem column screening tool

“…6 Analysis of complex mixtures of closely related stereoisomers has long relied on the use of fixed tandem column arrangements, a typical approach being the pairing of an achiral column (to separate diastereomers) with a chiral column (to separate enantiomers). [7][8][9] A certain inconvenience is involved in the setup and use of tandem column arrangements, as mechanical plumbing of the assembly is required, and the two columns used in the study become unavailable for conventional single column use while in the tandem arrangement. To overcome these limitations and to create a tool for systematic exploration of tandem column approaches for solving multicomponent chiral separation problems, we have developed a modification of the Berger analytical supercritical fluid chromatography (SFC) system that allows for software-controlled selection of 25 different tandem column arrangements and 10 different single column arrangements, thereby affording a convenient tool for developing and utilizing tandem SFC separation methods.…”