Control of Enantiomeric Purity of Drugs

Page: 994

M. Dolezalova and M. Tkaczykova

State Institute for Drug Control, Prague


Due to the importance of stereoisomerism for drug efficacy and safety and due to the strict policy of regulatory authorities, pharmaceutical companies tend to produce chiral drugs in single enantiomeric forms. In drug control, the undesirable stereoisomers should be considered in the same manner as other organic impurities. The potential of enantioselective liquid-phase separation methods in determination of the enantiomeric purity is demonstrated for three structurally related drugs, levodopa, methyldopa and carbidopa. Direct HPLC and capillary electrophoretic separations of the enantiomers of interest with the use of recently introduced chiral selectors, teicoplanin and sulfobutyl ether b-cyclodextrin, are described. In addition, ligand-exchange liquid chromatography with N,N-dimethyl-L-phenylalanine or L-phenylalanine in mobile phase is discussed. Results of measurement of optical rotation according to the European Pharmacopoeia are mentioned and inapplicability of polarimetric methods to assessment of enantiomeric impurities (D-isomers) at levels lower than 2 % is shown.


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