Simultaneous separation of the enantiomers of cizolirtine and its degradation products by capillary electrophoresis.
The simultaneous enantioselective separation of (+/-)-cizolirtine and its impurities: (+/-)-N-desmethylcizolirtine, (+/-)-cizolirtine-N-oxide and (+/- )-5-(alpha-hydroxybenzyl)-1-methylpyrazole was investigated by capillary electrophoresis. Electrokinetic chromatography with carboxymethyl-beta-CD (CM-beta-CD) and sulfobutyl-ether-beta-CD was tried, showing good enantioseparation but poor chemical selectivity. The four racemic pairs were baseline separated, in a single run, by cyclodextrin-modified micellar electrokinetic chromatography. The migration buffer composition was: (60 mM hydroxypropyl-beta-cyclodextrin-150 mM sodium dodecyl sulfate-50 mM disodium tetraborate, pH 9.2, in water)-butanol 95:5, v/v). Work was done to determine the effect of buffer components and their optimal concentration on selectivity. The method was validated with respect to enantioselectivity of cizolirtine as well as its degradation products and separation selectivity between the different components. Linearity, limit of detection, limit of quantitation and precision were also determined. This method is suitable for the enantiomeric purity determination and stability control of cizolirtine (racemic mixture or enantiomers) and its degradation products. Examples of electropherograms of (R)-cizolirtine degraded under stressed conditions are shown.
Gómez-Gomar
A
A
Medicinal Chemistry Department, Laboratorios Dr. Esteve S.A., Barcelona, Spain. agomez@esteve.es
Ortega
E
E
Calvet
C
C
Mercé
R
R
Frigola
J
J
D020374:Chromatography, Micellar Electrokinetic Capillary; D019075:Electrophoresis, Capillary / Q000379:methods*; D006868:Hydrolysis; D009930:Organic Chemicals; D011720:Pyrazoles / Q000737:chemistry / Q000302:isolation & purification*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012997:Solvents; D013237:Stereoisomerism
D009930:Organic Chemicals; D011720:Pyrazoles; D012997:Solvents; C075798:cizolirtine