Enantiomeric discrimination and quantification of Zolmitriptan by 1H NMR spectroscopy using (R)-(-)-α-Methoxy phenyl acetic acid as chiral solvating agent

Ramisetti Nageswara Rao, Konda

Abstract

A simple, accurate, precise, convenient and economical 1H-NMR method for enantiomeric resolution and quantitative determination of the two enantiomeric forms of Zolmitriptan utilizing (R)-(-)-α-methoxy phenyl acetic acid ((R)-MPA) as a chiral solvating agent is developed. Optimal experimental conditions were evaluated by studying the interaction of substrate with different concentrations of chiral solvating agents viz., (R)-(-)-α-methoxy phenyl acetic acid ((R)-MPA), (R)-(+)-α-Methoxy-α-trifluoromethyl phenyl acetic acid ((R)-MTPA), (S)-(-)-2,2,2- trifluoro-1-(9-anthryl)ethanol ((S)-TFAE), and (S)-(-)-1,1'-(2-naphthol) ((S)-BINOL) for 1H NMR spectroscopic resolution and determination of Zolmitriptan enantiomers in bulk drugs. Effects of the nature and mole ratio of CSA to analyte on enantiomeric discrimination were investigated. Among different chiral selectors (R)-MPA showed the highest resolution of 1H-NMR signals of Zolmitriptan enantiomers. Hydrogen bonding interaction between the analyte and CSA was the driving force for desired resolution. A mechanism was proposed to explain the interactions between ZMT enantiomers and (R)-MPA. The mole ratio of (R)-MPA with each of the enantiomers of analyte was determined by Job plots which were used to study the complex formation between (R)-MPA and analytes. The method was validated in terms of LOD, LOQ, linearity and recovery. The method was applied successfully to determine the enantiomeric purity of ZMT in bulk drugs.