Design of experiments for enantiomeric ...
Document type :
Article dans une revue scientifique
PMID :
Permalink :
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 - U 995 [LIRIC]
Lille Inflammation Research International Center - U 995 [LIRIC]
Lille Inflammation Research International Center (LIRIC) - U995
Vaccher, Claude [Auteur]
Yous, Said [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Lipka, Emmanuelle [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Lille Inflammation Research International Center - U 995 [LIRIC]
Lille Inflammation Research International Center (LIRIC) - U995
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
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 >
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
CHU Lille
Inserm
Collections :
Submission date :
2019-02-26T17:11:47Z