Enantiomeric Purity Determination Of Chiral Drugs By CSPs Combining With Pre-Column Derivation

High performance liqiud chromatography(HPLC) is a fast and effictive method of separating enantiomers of chiral material. Chiral stationary phases (CSPs) especially the Pirkle-type CSPs were frequently used in the chiral HPLC separation. The Pirkle-type CSPs have been used widely in determining enantiomertic purity of chiral drugs and in preparing enantiomers or intermediates of chiral drugs.The Pirkle-type CSPs have some limitation to application because of their special structures, though many enantiomers can be separated by the CSPs. The principle of pre-column derivation combining with separation on CSPs was applied in this paper. The chiral drug was derived according to the CSPs' characteristic,and then the enantiomers' derivates were separated by the CSPs. There may be much more difference in the interaction between the two enantiomers' derivates and the CSPs after the derivation. The enantiomers of some chiral drugs such as Mandelic acid andα-Phenylethylamine can be separated by this method though they can't be originally on the CSPs. This method of the derivation was convenient, fast and enantiomeric stable. There was little racemization in the derivation which have the amide product. There could be many reagents chosen for the derivation. This method of derivation was very practical.Normal-phase chromatographic model was employed for the enantionmeric separation of derivatives on the CSPs. The effects of chromatographic conditions such as mobile phases and temperature to chiral recognition of the derivatives had been investigated. The derivatives were primely resolved on the Pirkle-type CSPs in the optimal chromatographic conditions. The chiral recognition mechanisms have been discussed further according to the relative thermodynamic parameters. The chiral recognition models of the enantiomers on CSPs were also predicted by the comparison research of enantioseparation thermodynamic data.According to the definition of optical purity and the peak area proportional to the quantity of the material, the HPLC method for determining the optical purity of enantiomers was established. Some chiral drugs with different optical purities were determined by the HPLC and compared with those by polarimeter, a new chiral HPLC method for determinig optimal purties was founded. This method of HPLC meant much in the real-time control of chiral drugs in asymmetric reactions and production.