Omeprazole preparative enantiomer separation

Fig. 19. Preparative enantiomer separation of omeprazole on Chiralpak AS (column 230 mm x48 mm i.d., dp = 20 pm) eluent isopropanol/ethanol (70 30, v/v), injected amount -120 mg flow 100 ml min" top trace polarimetric detection first eluting enantiomer positive signal, second eluting enantiomer negative signal bottom trace UV detection 234 nm.

Omeprazole can be made by reaction of a substituted diaminobenzene to make the benzoimidazole [38]. Alkylation of the thiol gives the sulfide which is then oxidized to the sulfoxide, omeprazole. The omeprazole can be separated into the two enantiomers. Preferably, asymmetric oxidation of the sulfide is done to selectively prepare the S enantiomer, esomeprazole. 

Berzas Nevado, J. J., Castaneda Penalvo, G., and Rodriguez Dorado, R. M. (2005). Method development and validation for the separation and determination of omeprazole enantiomers in pharmaceutical preparations by capillary electrophoresis. Anal. Chim. Acta 533, 127-133. 

Berzas Nevado et al. [138] developed a new capillary zone electrophoresis method for the separation of omeprazole enantiomers. Methyl-/ -cyclodextrin was chosen as the chiral selector, and several parameters, such as cyclodextrin structure and concentration, buffer concentration, pH, and capillary temperature were investigated to optimize separation and run times. Analysis time, shorter than 8 min was found using a background electrolyte solution consisting of 40 mM phosphate buffer adjusted to pH 2.2, 30 mM /1-cyclodextrin and 5 mM sodium disulfide, hydrodynamic injection, and 15 kV separation voltage. Detection limits were evaluated on the basis of baseline noise and were established 0.31 mg/1 for the omeprazole enantiomers. The method was applied to pharmaceutical preparations with recoveries between 84% and 104% of the labeled contents. 

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