Investigation of racemisation of the enantiomers of glitazone drug compounds at different pH using chiral HPLC and chiral CE
Autor: | Babak Jamali, Ole Nordfang, Steen Honoré Hansen, Inga Bjørnsdottir |
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Rok vydání: | 2008 |
Předmět: |
Drug
Time Factors Chemistry Pharmaceutical media_common.quotation_subject Clinical Biochemistry Pharmaceutical Science Context (language use) Stereoisomerism High-performance liquid chromatography Analytical Chemistry Rosiglitazone Capillary electrophoresis Drug Stability Drug Discovery Technology Pharmaceutical Organic chemistry Chromatography High Pressure Liquid Spectroscopy media_common Chromatography Molecular Structure Pioglitazone Chemistry Electrophoresis Capillary Hydrogen-Ion Concentration Solutions Chiral column chromatography Racemic mixture Thiazolidinediones Enantiomer Algorithms |
Zdroj: | Journal of Pharmaceutical and Biomedical Analysis. 46:82-87 |
ISSN: | 0731-7085 |
Popis: | Drug enantiomers can have biologically distinct interactions within the biological system and consequently different pharmacological or toxicological effects. Development of a better and safer drug product may be considered if one of the enantiomers has a significantly better effect/side effect ratio than the other. Investigation of the single enantiomers in a racemic mixture could be valuable in order to investigate whether the single enantiomers demonstrate difference in pharmacological effect and/or fewer side effects versus the racemic mixture. In this context investigation of a possible racemisation of the pure enantiomers is very important. In order to obtain the enantiomers of the racemic pioglitazone and the racemic rosiglitazone an HPLC method for chiral separation was developed. Using this method the R and S enantiomers were separated and the method was used to collect each enantiomer for investigation of racemisation process. The racemisation of the enantiomers of pioglitazone and rosiglitazone was investigated at pH 2.5, 7.4 and 9.3 using a chiral CE system. At pH 2.5 all enantiomers showed a slow racemisation. After 192 h (8 days) at 37 degrees C the ratio of the enantiomers in the mixture for all four isolated enantiomers was approximately 2 to 1 and after 1440 h (30 days) full racemisation was observed. The racemisation speed increased with increasing pH. At pH 7.4 the ratio of the enantiomers in the mixtures was approximately 2 to 1 already after 10h. Full racemisation was observed within 48 h (2 days) at pH 7.4 and within 24 h at pH 9.3. These investigations have shown that it is possible to separate and isolate the enantiomers from a racemic mixture of glitazone drug substance and perform racemisation studies on each enantiomer. |
Databáze: | OpenAIRE |
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