Synthesis of a Series of Quinoline-Based New Chiral Reagent and its Application in Separation of Racemic Mexiletine followed by Liquid Chromatography and Confirmation of Results Using Molecular Modelling; A Complete Study

• Published in: Asian journal of chemistry 2024-01, Vol.36 (2), p.404-410
• Main Authors: Solanki, M., Sehlangia, S., Talismanov, V.S., Damayanthi, A., Patel, M. S., Shrivastava, S., Alwera, S.
• Format: Article
• Language: English
• ISSN: 0970-7077; 0975-427X
• DOI: 10.14233/ajchem.2024.30926

In present work, L-valine-based new chiral derivatives were prepared by introducing hydrophobic groups. The prepared derivatives were then used to prepare quinoline-based chiral reagents under mild amidation reaction and esterification reaction. Spectroscopic  techniques, such as HRMS, FT-IR, 1H NMR and CHNS analysis, were used to characterize the synthesized chiral reagents. The  synthesized series of reagents was then used to derivatize diastereomers of racemic mexiletine and these diastereomers were  separated using the RP-HPLC (a derivatization approach of enantioseparation). The mobile phase for the analysis consisted of  acetonitrile and buffer solution. The impact of modifying mobile phase pH and concentrations was optimized to separate  diastereomers. The lowest energy-minimize optimized diastereomer structures, as well as the design of separation processes and  elution orders, were also developed through the use of density functional theory (DFT) calculations. Following ICH guidelines, the limits of detection (0.161 ng/mL) and quantification (0.483 ng/mL) were determined, together with the retention-factor (k), selectivity-factor  (α), resolution-factor (RS) and technique validation.