Chiral separations of metoprolol and some analogs with carbon dioxide on chiralcel OD and chiralpak AD stationary phases. Use of chemometrics |
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Authors: | S Svensson A Karlsson O Gyllenhaal J Vessman |
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Institution: | 1. Analytical Chemistry, Astra Zeneca R & D M?lndal, 431 83, M?lndal, Sweden
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Abstract: | Summary The influence of methanol concentration, column temperature, and column back-pressure on the enantios-electivity of the separation
of eighteen amino alcohols in supercritical-fluid chromatography has been investigated by use of statistical experimental
design. The enantioselective retention of the amino alcohols was studied using Chiralcel OD and Chiralpak AD as the chiral
stationary phases and the experimental responses obtained—retention factors (k) and selectivity factors (α)—were evaluated by use of the partial least squares algorithm. The performance of the columns
was compared and the enantioselectivity of the Chiralcel OD column was found to be superior. Almost all the racemic amino
alcohols tested were separated and separation factors as high as 4.5 were obtained by use of the Chiralcel OD column.
Experimental results from a factorial design with three centerpoints resulted in a statistical model based on linear terms
only. The first-eluted enantiomers, which, when identified, were found to be theR forms, had similar retention times, whereas the retention times of theS forms were more varied. The column temperature had a greater effect on enantioselectivity than methanol content. Changes
in the system back-pressure had no significant influence on enantioselectivity.
The results obtained from the factorial design were used to predictk and α. Differences between predicted and experimental data were less than 10%.
The effect on enantioselectivity of protolytic mobile phase additives, e. g. dimethyloctylamine, acetic acid, and trifluoroacetic
acid, and of mobile-phase flow-rate, were also studied, as was the effect of solute structure. The position of substituents
on the aromatic ring, type of alkyl group attached to the nitrogen atom, and the number of methylene groups between the stereogenic
center and the nitrogen atom all affected enantioselectivity.
The chromatographic system developed could be used to determine enantiomeric purity even if the chiral impurity eluted after
the main peak. |
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Keywords: | Supercritical-fluid chromatography Enantiomer separation Amino alcohols Statistical experimental design |
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