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Original Articles

Direct Liquid Chromatographic Resolution of Acidic Drugs Using a Chiral α1-Acid Glycoprotein Column (Enantiopac®)

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Pages 621-639 | Published online: 19 Dec 2006
 

Abstract

A chiral α1-acid glycoprotein column (EnantioPac®) has been used for the separation of the enantiomers of some acidic (ibuprofen, ketoprofen, naproxen, 2-phenoxypropionic acid, bendroflumethiazide, ethotoin and hexobarbital) and basic drugs (disopyramide and RAC 109).

The column is prepared by immobilization of the human plasma protein α1-acid glycoprotein on silica particles. The retention and the enantioselectivity of the solutes can easily be regulated by the addition of the tertiary amine N,N,-dimethyloctylamine (DMOA) to the mobile phase. DMOA decreases the retention and the enantioselectivity of the weaker acids, whereas the retention and the enantioselectivity of the stronger acids increase drastically with increasing DMOA concentration.

The influence of column temperatures between 25 and 80°C on the separation factor, separation efficiency and the resolution was also evaluated. Stability studies indicate that the α1-acid glycoprotein column (EnantioPac®) is very stable. It can be used at elevated temperatures, it tolerates pure 2-propanol and has been stored in a water-2-propanol mixture long periods (12 months) with < 10% changes of the capacity and separation factors.

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