Abstract
Enantioseparation of (RS)-ketamine has been achieved in the form of its diastereomeric hydrazones. A new chiral reagent was synthesized from enantiomerically pure (S)-levofloxacin by converting its carboxyl group into a hydrazide derivative: the reagent provided a reaction site for the ketonic group present in (RS)-ketamine. Because of the structural feature of the chiral reagent formation of diastereomeric hydrazones of (RS)-ketamine was successful without protection of its amino group. The diastereomeric hydrazones were separated on a reversed-phase C18 column with a mobile phase consisting of MeCN and 0.1% TFA under gradient elution from 35 to 65% of MeCN. The limit of detection was found to be 3.2 and 3.4 nmol for first and second eluting diastereomeric hydrazones, respectively. The separation mechanism and elution order of the diastereomeric hydrazones were proposed and supported by developing the geometry optimized ‘lowest energy’ structures of the two diastereomeric hydrazones using DFT-based Gaussian software.
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Acknowledgements
The authors are grateful to the University Grants Commission, New Delhi, India, for awarding a senior research fellowship (to VKV). Thanks are also due to Alexander von Humboldt Stiftung, Bonn, Germany, for awarding a research fellowship and to the Indian Institute of Technology Roorkee, Roorkee, India, for granting leave of absence to (RB).
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The paper was prepared and submitted during RB’s stay at the University of Oldenburg.
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Vashistha, V.K., Martens, J. & Bhushan, R. Sensitive RP-HPLC Enantioseparation of (RS)-Ketamine via Chiral Derivatization Based on (S)-Levofloxacin. Chromatographia 80, 1501–1508 (2017). https://doi.org/10.1007/s10337-017-3367-2
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DOI: https://doi.org/10.1007/s10337-017-3367-2