title: Evaluation of (R)-(-)-α-methoxy phenyl acetic acid as a chiral shift reagent for resolution and determination of R and S enantiomers of modafinil in bulk drugs and formulations by 1H NMR spectroscopy.
abstract: (R)-(-)-α-Methoxy phenyl acetic acid, (S)-(-)-1,1'-(2-naphthol), and (R)-(+)-α-methoxy-α-trifluoromethyl phenyl acetic acid were evaluated as chiral shift reagents (CSRs) for (1)H NMR spectroscopic resolution and determination of R and S enantiomers of modafinil (MDL) in bulk drugs and formulations. Effects of the nature of CSR and the weight ratio of substrate to shift reagent on enantiomeric discrimination were investigated. Intramolecular and intermolecular hydrogen bonding interactions between the drug and the CSR seem to be the driving force for desired resolution. A mechanism was proposed to explain the interactions between (R, S)-enantiomers of MDL and (R)-(-)-α-methoxy phenyl acetic acid. The method was validated and applied successfully to determine the enantiomeric purity of MDL in tablet formulations.
authors.affiliation: Analytical Chemistry Division, D215, Discovery Laboratory, Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500 607, India. rnrao55@yahoo.com
authors.forename: Ramisetti Nageswara
authors.initials: RN
authors.lastname: Rao
authors.forename: Bondigalla
authors.initials: B
authors.lastname: Ramachandra
authors.forename: Kondapalli
authors.initials: K
authors.lastname: Santhakumar
mesh_terms: D001559:Benzhydryl Compounds / Q000032:analysis* / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D006860:Hydrogen Bonding; D007202:Indicators and Reagents / Q000737:chemistry; D057230:Limit of Detection; D016014:Linear Models; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D000077408:Modafinil; D008968:Molecular Conformation; D008970:Molecular Weight; D010648:Phenylacetates / Q000737:chemistry*; D015203:Reproducibility of Results; D012997:Solvents / Q000737:chemistry; D013237:Stereoisomerism; D013607:Tablets
chemical_list: D001559:Benzhydryl Compounds; D007202:Indicators and Reagents; D010648:Phenylacetates; D012997:Solvents; D013607:Tablets; C023699:3-methoxyphenylacetic acid; D000077408:Modafinil