A validated chiral liquid chromatographic method for the enantiomeric separation of safinamide mesilate, a new anti-Parkinson drug

Abstract

A enantioselective reversed-phase high performance liquid chromatographic method was developed for the enantiomeric resolution of safinamide mesilate, 2( S)-[4-(3-fluorobenzyloxy)benzylamino] propionamide methanesulfonate, a neuroprotectant with antiparkinsonian and anticonvulsant activity for the treatment of Parkinson disease. The enantiomers of safinamide mesilate were baseline resolved on a Chiralcel OD-RH (150 mm × 4.6 mm, 5 μm) column using a mobile phase system containing 300 mM sodium di-hydrogen phosphate buffer (pH 3.0):methanol:acetonitrile (65:25:10, v/v/v). The resolution between the enantiomers was not less than 3.0. The pH value of buffer solution in the mobile phase has played a key role in enhancing chromatographic efficiency and resolution between the enantiomers. The developed method was validated and proved to be robust. The limit of detection and limit of quantification of ( R)-enantiomer were found to be 15 and 50 ng/mL, respectively, for 20 μL injection volume. The percentage recovery of ( R)-enantiomer was ranged from 94.2 to 103.7 in bulk drug samples of safinamide mesilate. The sample solution and mobile phase were found to be stable at least for 48 h. The final optimized method was successfully applied to separate ( R)-enantiomer from safinamide mesilate and was proven to be reproducible and accurate for the quantitative determination of ( R)-enantiomer in bulk drugs.