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8226920 
Journal Article 
Chiral HPLC separation of rosiglitazone and its main metabolites and studies on their racemization 
Calixto, LA; Bonato, PS 
2013 
Yes 
Chromatographia
ISSN: 0009-5893
EISSN: 1612-1112 
SPRINGER HEIDELBERG 
HEIDELBERG 
76 
23-24 
1613-1621 
English 
WOS:000327433500006 
Rosiglitazone (RSG) is marketed as a racemic mixture although the antidiabetic activity is essentially related to the (S)-enantiomer. The chiral center has an adjacent carbonyl group; therefore, the (R)-enantiomer could be transformed to the (S)-enantiomer or vice versa by keto-enolic tautomerism. The literature indicates that this racemization is slow enough to allow the evaluation of the properties of the isolated enantiomers. However, there is no information about the enantioselective kinetic disposition and metabolism of RSG. Additionally, there are no studies on the racemization of its metabolites. Considering these facts, a chiral HPLC method was developed and used for the first time to study the racemization of RSG and its main metabolites. Different conditions, including those used to evaluate the in vitro enantioselective metabolism, were employed. The simultaneous chiral separation of RSG and metabolites was achieved on a Chiralcel OJ-H column by employing methanol/ethanol (90:10, v/v) as mobile phase. The racemization studies showed that the half-life of RSG decreased more than 30 times when the temperature increased from 4 to 37 C. It was also observed that the half-life of RSG changed from approximately 20 h at pH 3.5 to approximately 2 h at pH 7.4. The same profile was observed for its metabolites. Organic solvents and UV light did not present influence on the racemization process. In addition, a Complete Factorial Design was conducted to evaluate the influence of some parameters that can be changed during an in vitro metabolism study. The results obtained showed that the racemization occurs under in vitro metabolism conditions. © 2013 Springer-Verlag Berlin Heidelberg. 
Chiral separation; Column liquid chromatography; In vitro metabolism; Metabolites; Racemization study; Rosiglitazone