Comparison of CZE, MEKC, MEEKC and non-aqueous capillary electrophoresis for the determination of impurities in bromazepam

J Pharm Biomed Anal. 2005 Sep 1;39(1-2):322-7. doi: 10.1016/j.jpba.2005.03.017.


The purpose of the present investigation was to develop a test for related substances in the benzodiazepine drug substance bromazepam based on capillary electrophoresis (CE). A final method for the determination of impurities in bromazepam is based on non-aqueous capillary electrophoresis (NACE). Five modes of capillary electrophoresis were investigated and compared for the said purpose. All the CE systems investigated make use of running buffers at low pH in order to protonate the analytes. A low pH of the running buffers was needed as the pK(a) values of benzodiazepines in general are in the range from 1.3 to 4.6. Dynamically coated capillaries were used to overcome the low electro-osmotic flow at low pH in the aqueous buffers investigated. CZE with and without dynamical coating of the internal surface of the fused capillaries was compared and also micellar electrokinetic chromatography (MEKC) as well as microemulsion electrokinetic chromatography (MEEKC) performed in dynamically coated capillaries were investigated. The NACE was chosen as the best technique as the low solubility of the benzodiazepines in water is easily overcome. The NACE system showed good selectivity and detectability for the substances investigated and the limit of quantitation for the impurities corresponded to 0.05% of the drug substance. Linearity was good.

Publication types

  • Comparative Study
  • Validation Study

MeSH terms

  • Bromazepam / chemistry*
  • Bromazepam / isolation & purification
  • Electrophoresis, Capillary / methods*
  • Sensitivity and Specificity


  • Bromazepam