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A Chiral Generic Strategy for Enantioseparation of Acidic and Basic Drugs Using Short End Injection Capillary Electrophoresis: Application to Design of Experiment

  • Hassan Y. Aboul-Enein
  • Ahmed M. Abdel-Megied
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1972)

Abstract

The present work describes a capillary electrophoretic (CE) generic strategy used for chiral enantioseparation of Fluconazole (as an example of acidic drugs) and donepezil (as an example of basic drugs). Several modified cyclodextrins (CDs) were applied for enantioseparation of racemates such as highly sulfated α, γ CDs, hydroxyl propyl-β-CD, and sulfobutyl ether-β-CD. The starting screening conditions consist of 50 mM phosphate–triethanolamine buffer at pH 2.5, an applied voltage of 15 kV, and a temperature of 25 °C. The design of experiment (DOE) was based on a full factorial design of the crucial two factors (pH and %CD) at three levels, to make a total of nine (32) experiments with high, intermediate, and low values for both factors. Evaluation of the proposed strategy pointed out that best resolution was obtained at pH 2.5 for the investigated racemates using low percentages of HS-γ-CD, while SBE-β-CD was the most successful chiral selector offering acceptable resolution, with best separation at low pH values and at higher %CD within 10 min runtime. Regression study showed that the linear model shows a significant lack of fit for all chiral selectors, anticipating that higher orders of the factors are most likely to be present in the equation with possible interactions.

Key words

Enantiomers Highly sulfated α,γ-CDs Design of experimental Fluconazole Donepezil 

References

  1. 1.
    Muller T (2007) Rivastigmine in the treatment of patients with Alzheimer’s disease. Neuropsychiatr Dis Treat 3(2):211–218CrossRefGoogle Scholar
  2. 2.
    Sugimoto H et al (2000) Donepezil hydrochloride (E2020) and other acetylcholinesterase inhibitors. Curr Med Chem 7(3):303–339CrossRefGoogle Scholar
  3. 3.
    Matsui K et al (1999) Simultaneous determination of donepezil (aricept) enantiomers in human plasma by liquid chromatography-electrospray tandem mass spectrometry. J Chromatogr B Biomed Sci Appl 729(1–2):147–155CrossRefGoogle Scholar
  4. 4.
    Crego AL, Marina ML, Lavandera JL (2001) Optimization of the separation of a group of antifungals by capillary zone electrophoresis. J Chromatogr A 917(1–2):337–345CrossRefGoogle Scholar
  5. 5.
    Lu J et al (2015) Stereoselective metabolism of donepezil and steady-state plasma concentrations of S-donepezil based on CYP2D6 polymorphisms in the therapeutic responses of Han Chinese patients with Alzheimer’s disease. J Pharmacol Sci 129(3):188–195CrossRefGoogle Scholar
  6. 6.
    Bolognesi ML et al (2004) Design, synthesis, and biological evaluation of conformationally restricted rivastigmine analogues. J Med Chem 47:5945–5952CrossRefGoogle Scholar
  7. 7.
    Tomaszewski J, Rumore MM (1994) Stereoisomeric drugs: FDA’s policy statement and the impact on drug development. Drug Dev Ind Pharm 20:119–139CrossRefGoogle Scholar
  8. 8.
    Francotte ER (2001) Enantioselective chromatography as a powerful alternative for the preparation of drug enantiomers. J Chromatogr A 906(1–2):379–397CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Hassan Y. Aboul-Enein
    • 1
  • Ahmed M. Abdel-Megied
    • 2
  1. 1.Pharmaceutical and Medicinal Chemistry Department, Pharmaceutical and Drug Industries Research DivisionNational Research CenterDokki, CairoEgypt
  2. 2.Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy and Pharmaceutical ManufacturingKafrelsheikh UniversityKafrelsheikh CityEgypt

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