Title :

Design of experiments for enantiomeric separation in supercritical fluid chromatography

Author(s) :

Landagaray, Elodie [Auteur]
Vaccher, Claude [Auteur]
Yous, Said [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172

Lipka, Emmanuelle [Auteur]
Lille Inflammation Research International Center (LIRIC) - U995
Lille Inflammation Research International Center - U 995 [LIRIC]
Lille Inflammation Research International Center - U 995 [LIRIC]

Journal title :

Journal of pharmaceutical and biomedical analysis

Abbreviated title :

J. Pharm. Biomed. Anal.

Volume number :

120

Pages :

297-305

Publication date :

2016-02-20

ISSN :

0731-7085

English keyword(s) :

Polysaccharide chiral stationary phase
Melatoninergic ligands
Naphtalens
Optimization
Chiral separation
Experimental design

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

A new chiral melatoninergic ligand, potentially successor of Valdoxan(®), presenting an improved pharmacological profile with regard to agomelatine, was chosen as a probe for a supercritical fluid chromatographic separation ...
Show more >A new chiral melatoninergic ligand, potentially successor of Valdoxan(®), presenting an improved pharmacological profile with regard to agomelatine, was chosen as a probe for a supercritical fluid chromatographic separation carried-out on an amylose tris[(S)-1-α-methylbenzylcarbamate] based stationary phase. The goal of this work was to optimize simultaneously three factors identified to have a significant influence to obtain the best resolution in the shortest analysis time (i.e., retention time of the second eluting enantiomer) for this chiral compound. For this purpose a central circumscribed composite (CCC) design was developed with three factors: the flow-rate, the pressure outlet and the percentage of ethanol to optimize of two responses: shortest analysis time and best resolution. The optimal conditions obtained via the optimizer mode of the software (using the Nelder-Mead method) i.e., CO2/EtOH 86:14 (v:v), 104bar, 3.2mLmin(-1) at 35°C lead to a resolution of 3.27 in less than 6min. These conditions were transposed to a preparative scale where a concentrated methanolic solution of 40mM was injected with a sample loop of 100μL. This step allowed to separate an amount of around 65mg of racemic melatonin ligand in only 3h with impressive yields (97%) and enantiomeric excess (99.5%).Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
CHU Lille
Inserm

Collections :

• Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA) - ULR 7365
• Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
• Lille Neurosciences & Cognition (LilNCog) - U 1172

Submission date :

2019-02-26T17:11:47Z