Enantioseparation of novel COX-2 anti-inflammatory drugs by capillary electrophoresis using single and dual cyclodextrin systems.
A capillary electrophoresis method was developed for the enantioseparation of three novel cyclooxygenase-2 (COX-2) inhibitor drugs (E-6259, E-6036 and E-6087) with anti-inflammatory and analgesic activities using sulfobutyl ether-beta-cyclodextrin (SBE-beta-CD) as a chiral selector. The use of 50 mM sodium tetraborate at pH 9.2 with 30% v/v methanol, containing 7.1 mM SBE-beta-CD, as a background electrolyte (BGE) allowed the complete enantioseparation of the three neutral racemic mixtures (resolution = 2.4, 3.0 and 8.7, respectively) and their corresponding metabolites (oxidation products) in a single run. Migration times were shortened with some loss of enantioresolution by adding 1.75 mM dimethyl-beta-cyclodextrin (DM-beta-CD) to the previous BGE (dual CD system). The reversal of the migration order of E-6259 enantiomers in the dual CD system was also studied. Furthermore, the addition of DM-beta-CD to the BGE introduced a new chemoselectivity in the system that allowed E-6259 to be separated from the structurally similar compound E-6036.
Laboratorios Dr. Esteve S.A., Medicinal Chemistry Department, Av. Mare de Déu de Montserrat, 221, E-08041 Barcelona, Spain.
Carmen
C
Calvet
Rosa
R
Cuberes
Carlos
C
Pérez-Maseda
Jordi
J
Frigola
D020374:Chromatography, Micellar Electrokinetic Capillary; D003505:Cyclodextrins; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000032:analysis / Q000302:isolation & purification*; D019075:Electrophoresis, Capillary / Q000379:methods*; D004987:Ethers; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D000432:Methanol; D011451:Prostaglandin-Endoperoxide Synthases; D011720:Pyrazoles; D013237:Stereoisomerism; D013449:Sulfonamides; D047392:beta-Cyclodextrins; D000096926:Benzenesulfonamides
D003505:Cyclodextrins; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D004987:Ethers; D007527:Isoenzymes; D000432:Methanol; D011451:Prostaglandin-Endoperoxide Synthases; D011720:Pyrazoles; D013449:Sulfonamides; D047392:beta-Cyclodextrins; C093196:SBE4-beta-cyclodextrin; C427706:enflicoxib; D000096926:Benzenesulfonamides