Chromatographic separation of the Enantiomer of Chiral active pharmaceutical ingredients using molecular imprinting technology

Abstract

Chromatographic separation of enantiomers is of prime importance in the development of active pharmaceutical ingredients. As a result of an intensive advancement in chiral separation technologies, several hundreds of chiral stationary phases (CSP) for liquid chromatography (LC) are now commercially available. But these columns are expensive and the analysis cost is also high. So efficient and cost effective molecularly imprinted column was developed and an efficient method was developed. In this work, molecular imprinting technology was employed to prepare a specific affinity sorbent for the resolution of drug enantiomers of Cathine, Phenylephrine, Pseudoephedrine, Ephedrine, Ritalinic acid and N-Methylephedrine. The molecularly imprinted polymer (MIP) was prepared by non-covalent molecular imprinting with either (+) or (-)-chiral drug molecule as a template on a polymer formed by copolymerization of methacrylic acid and ethylene glycol dimethacrylate (EGDMA)in presence of 2,2?-Azo-bisisobutyronitrile (AIBN) as the initiator in chloroform, at 5°C and under UV radiation. The resulting MIP was dried, ground and size reduced to uniform powder. The physical as well as the chemical properties of the polymeric particles so formed was carried out using Scanning Electron Microscopy (SEM), Brunauer, Emmett, Teller (BET) and particle size analysis. The powder was then slurry packed into the column and the template was washed off using suitable solvents. LC method was developed with polar organic mobile phases, and the influence of parameters such as temperature, the percentage of polar organic modifier, the nature and concentration of the acidic additive acetic acid in the mobile phase was first evaluated. The developed method was then fully validated as per International Conference on Harmonization (ICH) guidelines. The efficiency of the MIP column was compared with the commercially available CSP column and it was proved that the MIP column has greater resolution, precision, accuracy and better impurity detection.