Determination of enantiomeric purity of a novel COX-2 anti-inflammatory drug by capillary electrophoresis using single and dual cyclodextrin systems.
E-6087 is the most advanced compound among the cyclooxygenase-2 (COX-2) inhibitor drugs developed in our company. Its activity is mainly associated with the S(-)-enantiomer (E-6232), whereas the R(-)-enantiomer (E-6231) becomes an impurity whose content should be determined. Five main impurities and degradation products of E-6232 have been found (E-6144, E-6024, E-6072, E-6397 and E-6132), and some of them co-elute with the distomer when using a chiral high-performance liquid chromatography (HPLC) method. Consequently, we have optimized the separation of all the impurities from the two enantiomers of E-6087 by capillary electrophoresis (CE), in order to use the method for the enantiomeric purity determination of E-6232. The effect of the methanol (MeOH) content in the background electrolyte (BGE), the sulfobutyl ether-beta-cyclodextrin (SBE-beta-CD) and heptakis-(2,6-di-O-methyl)-beta-cyclodextrin (DM-beta-CD) concentration, and the capillary temperature have been studied. Separation of all compounds could be achieved in different systems, either in a single CD-system (with SBE-beta-CD) or in a dual CD-system (with DM-beta-CD as a neutral CD). By using the dual CD system a limit of detection (LOD) and a limit of quantitation (LOQ) of 0.03% and 0.1% of distomer, respectively, were achieved*.
Laboratorios Dr. Esteve S. A., Medicinal Chemistry Department, Barcelona, Spain. caparez@esteve.es
Carlos
C
Pérez-Maseda
Carme
C
Calvet
Rosa
R
Cuberes
Jordi
J
Frigola
D000893:Anti-Inflammatory Agents / Q000302:isolation & purification; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003505:Cyclodextrins; D016861:Cyclooxygenase Inhibitors / Q000302:isolation & purification*; D019075:Electrophoresis, Capillary / Q000379:methods*; D000432:Methanol; D011720:Pyrazoles / Q000302:isolation & purification*; D013237:Stereoisomerism; D013449:Sulfonamides / Q000302:isolation & purification*; D013696:Temperature; D000096926:Benzenesulfonamides
D000893:Anti-Inflammatory Agents; D003505:Cyclodextrins; D016861:Cyclooxygenase Inhibitors; D000432:Methanol; D011720:Pyrazoles; D013449:Sulfonamides; C427706:enflicoxib; D000096926:Benzenesulfonamides