Screening approach for chiral separation of pharmaceuticals: IV. Polar organic solvent chromatography

The aim of this work is to determine generic screening conditions and an initial simple separation strategy allowing the rapid separation of drug enantiomers in polar organic solvent chromatography (POSC). Four cellulose/amylose-based stationary phases were investigated in detail using two mobile phase basis solvents commonly applied in this mode, i.e. acetonitrile and methanol. Polar mode is interesting for use in purification of enantiomers. In a first step, the parameters potentially influencing the separation, such as addition of an alcohol to the polar organic solvent or the type of mobile phase additive(s), were examined by means of experimental designs. Afterwards, the factors found most important are investigated in more detail. Results showed that the cellulose- and amylose-based stationary phases have very broad and complementary enantiorecognition abilities in the POSC mode. The type of organic solvent for the mobile phase appeared to have a dramatic influence on the quality of the separation. Based on the results, a screening strategy was proposed. Enantioseparation was observed in more than 85% of the tested compounds and analysis times of last eluted peak were usually below 10 min.