Referenced in: none

Automatically associated channels: Kir2.3

Title: Enantioseparation of pyroglutamide derivatives on polysaccharide based chiral stationary phases by high-performance liquid chromatography and supercritical fluid chromatography: a comparative study.

Authors: Davy Baudelet, Nadège Schifano-Faux, Alina Ghinet, Xavier Dezitter, Florent Barbotin, Philippe Gautret, Benoit Rigo, Philippe Chavatte, Régis Millet, Christophe Furman, Claude Vaccher, Emmanuelle Lipka

Journal, date & volume: J Chromatogr A, 2014 Oct 10 , 1363, 257-69

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/25039068

Abstract
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)-α-methylbenzylcarbamate) and cellulose tris (4-methylbenzoate) with various mobile phases consisted of either heptane/alcohol (ethanol and 2-propanol) or carbon dioxide/alcohol (methanol or ethanol) mixtures, were investigated. After analytical screenings, the best conditions were transposed, for compound 1, to semi-preparative scale. Each approach was fully validated to meet the International Conference on Harmonisation requirements and compared. 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), in terms 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 min versus 40 min per injection in SFC and HPLC, respectively) and yields (98% versus 71% in SFC and HPLC, respectively), the latter method proved its ecological superiority.