PhD Scientific Days 2019

Budapest, April 25–26, 2019

Chiral separation of guaifenesin, methocarbamol and mephenesin by liquid chromatography on polysaccharide-type stationary phases and by capillary electrophoresis using cyclodextrin selectors

Foroughbakhshfasaei, Mohammadhassan

Mohammadhassan Foroughbakhshfasaei, Gergő Tóth
Department of Pharmaceutical Chemistry, Semmelweis University, Budapest, Hungary

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Text of the abstract

Introduction: Guaifenesin, methocarbamol and mephenesin are structurally similar chiral alcohols used in therapy as expectorant and muscle relaxants. molecules contain one asymmetric center and consequently exist in two enantiomeric form. Due to the difference in the activity and pharmacokinetics of enantiomers in a chiral environment, development of efficient separation methods are crucial.
Aims: The aim of present study was to investigate the chiral separation ability of different polysaccharide-type CSPs in polar organic mode by liquid chromatography (LC) and different cyclodextrins by capillary electrophoresis (CE).
Methods: Enantioseparation capacity of six polysaccharide-type chiral selectors including amylose-based Lux Amylose-1 and Lux Amylose-2 as well as cellulose-based Lux Cellulose-1, Lux Cellulose-2, Lux Cellulose-3 and Lux Cellulose-4 were evaluated in polar organic mode using pure methanol and acetonitrile as the mobile phase by HPLC. Moreover, effects of column temperature on the separation process investigated in the temperature range of 10 - 40 °C. Using CE, several anionic cyclodextrins which differ in the cavity size, nature of the substituents and degree of substituents (DS), were screened for their ability to discriminate between the uncharged enantiomers.
Results: Among all investigated separation systems by HPLC baseline separation for all three investigated compounds achieved only using Lux Cellulose-1 with acetonitrile. In general, acetonitrile shown higher enantiorecognition ability than methanol. In spite of the very similar structures of the investigated drug many differences in chiral discrimination was found. Most successful separation processes achieved for mephenesin in comparison to two other compounds. Thermodynamic analysis based on classical van’t Hoff approach revealed usual enthalpy driven separation process in most conditions. Using CE, the best results were delivered by sulfobutylether-β-cyclodextrin DS 6.
Conclusion: Results of our work further underlines the importance and efficiency of polar organic mobile phase mode in enantioseparation process using polysaccharide-type columns in HPLC and using cyclodextrins as chiral selectors in CE.

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Doctoral School: Pharmaceutical science
Program: Experimental and Clinical Pharmacology
Supervisor: Dr. Gergő Tóth
E-mail address:
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