Molecular Modeling and Chiral Separation of Benzodiazepines by Capillary Electrophoresis Using Highly Sulfated Cyclodextrins


  • María Gabriela Vargas Martinez National Autonomous University of Mexico
  • Guillermo Ramírez Galicia Institute of Applied Chemistry, University of Papaloapan, Oaxaca



Chiral Separation, Benzodiazepines, Sulfated Cyclodextrins, Molecular Modeling


A capillary electrophoretic method for the chiral separation of the 3-chiral-1,4-benzodiazepines was developed. Enantiomeric resolution of oxazepam, lorazepam, temazepam, and lormetazepam was achieved using sulfated cyclodextrins (CD's) as chiral selectors. A 3-levels, 4-factors fractional factorial (34-2) design was applied to test 3 different CD's: heptakis-6-sulfato--cyclodextrin (HSCD), heptakis-(2,3-diacetyl-6-sulfato)--cyclodextrin (HDASCD), and heptakis-(2,3-dimethyl-6-sulfato)--cyclodextrin (HDMSCD). The CD type, its concentration, the pH of the electrolyte, and % organic modifier were tested as the factors in the experimental design. The highest resolution values were obtained using a 20 mM borate buffer, pH 9.0 with the addition of 5 % HSCD and 15 % methanol as an organic modifier. At these separation conditions, the equilibrium constants of the benzodiazepine-HSCD complex formation were calculated. A theoretical study of the interaction benzodiazepine-HSCD complex using semiempirical calculations is postulated.


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Author Biography

María Gabriela Vargas Martinez, National Autonomous University of Mexico

Department of Chemistry Sciences



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