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ENANTIOMERIC SEPARATION OF AN AMPA ANTAGONIST USING A CHIROBIOTIC T™ COLUMN WITH HPLC AND EVAPORATIVE LIGHT-SCATTERING DETECTION

A Chirobiotic T™ column was used for the direct separation of AMPA receptor antagonist LY293558 and the undesired enantiomer LY293559 in bulk drug substance. High performance liquid chromatography (HPLC) separation of the enantiomers was optimized using reversed phase and hydrophilic interaction chromatography (HILIC) by varying the organic composition of the mobile phase. Baseline resolution was achieved allowing accurate, trace level quantitation of the undesired enantiomer in the optically pure bulk material. Because the analytes lack a sufficient ultraviolet chromophore, an evaporative light-scattering detector (ELSD) was used to enhance detection. The ELSD was capable of obtaining detection limits as low as 0.1% of the undesired enantiomer. Additional experiments were conducted to assess the linearity, precision, and accuracy of the HPLC-ELSD system.