Dr. Emmanuelle LIPKA

High performance liquid chromatography versus supercritical fluid chromatography for the enantioseparation of pyroglutamide derivatives on polysaccharide based chiral stationary phases

Analytical enantioseparation of three pyroglutamide derivatives with pharmacological activity against the purinergic receptor P2X7, was run in both High Performance Liquid Chromatography and Supercritical Fluid Chromatography. Four polysaccharide based chiral stationary phases namely amylose and cellulose tris (3, 5-dimethylphenylcarbamate), amylose tris ((S)-a-methylbenzylcarbamate) and cellulose tris (4-methylbenzoate) with various mobile phases consisted of either heptane/alcohol or carbon dioxide/alcohol mixtures were investigated. After analytical screenings, best conditions were transposed to preparative scale. Each approach was fully validated to meet the International Conference on Harmonisation requirements and confronted. Whereas the limits of detection and quantification were near six fold better in HPLC than in SFC (respectively 0.20 and 0.66 µM versus 1.11 and 3.53 µM for one of the enantiomers), the latest method proved its indisputable “green-friendly” superiority in term of low solvent consumption (7.2 mL of EtOH versus 3.2 mL of EtOH plus 28.8 mL of toxic and inflammable heptane per injection in SFC and HPLC respectively), time effective cost (9 minutes versus 40 minutes per injection in SFC and HPLC respectively) and yields (98 % versus 71% in SFC and HPLC respectively).

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Thursday, March 8th
Dr. Emmanuelle LIPKA