PhD Scientific Days 2018

Budapest, April 19–20, 2018

A comparative enantioseparation of thalidomide class of drugs using polysaccharide-type stationary phases in lights of elution sequence and thermodynamic analysis in polar organic mode

Foroughbakhshfasaei, Mohammadhassan

Mohammadhassan Foroughbakhshfasaei1, Zoltán-István Szabó2, Béla Noszál1 Gergő Tóth1*

1Department of Pharmaceutical Chemistry, Semmelweis University, Budapest, Hungary
2Faculty of Pharmacy, University of Medicine and Pharmacy of Tîrgu Mureș, Romania

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Text of the abstract

Introduction: The enantiomers of thalidomide and its analogous (lenalidomide, pomalidomide and apremilast) have different biological effects. Therefore in-depth investigation of enantioseparation methods is crucial.
Aims: The aim of present study was to analyze different chromatographic parameters in order to evaluate their influence on enantioseparation capability including structure of chiral selectors, mobile phase constituent, flow rate and column temperature.
Methods: Enantioseparation capacity of six polysaccharide-type chiral selectors including amylose-based Chiralpak AD, Chiralpak IA, Chiralpak AS and Lux Amylose-2 as well as cellulose-based Chiralcel OD, Chiralcel OJ-H were evaluated in polar organic mode using pure MeOH, ACN, EtOH, 1-propanol and 2-propanol as the mobile phase. Elution order of enantiomers of all four drugs have been determined using enantiopure standards. Moreover effects of column temperature on the separation process investigated in the temperature range of 10 - 40 °C (in 5 °C increments) on retention, selectivity and resolution of enantiomers.
Results: In the present study we proved, that differences in the backbone, type of pendant groups and the nature of substituents in chiral selectors as well as properties of various mobile phases used such as their hydrogen bonding capabilities result in different enantioseparation capacity of each separating condition. In several cases chiral selector or mobile phase dependent reversal of elution orders was observed. Thermodynamic analysis based on classical van’t Hoff approach revealed usual enthalpy driven separation process in most conditions where increase of the temperature results in decreased selectivity however some unusual entropy driven separations were also observed.
Conclusion: Results of our work further underlines the importance of different chromatographic parameters and their influence on HPLC enantioseparation process using polysaccharide-type columns in polar organic mode.
Acknowledgements: The financial support from ÚNKP-17-4 New National Excellence Program of the Ministry of Human Capacity is highly appreciated

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Department of Pharmaceutical Chemistry, Semmelweis University, Budapest, Hungary
Supervisor: Gergő Tóth