Development of novel chiral capillary electrophoresis methods for the serotonin receptor (5-HT2A) antagonist MDL 100,907 (volinanserin) and for its key intermediate compound.
Enantioselective capillary electrophoretic methods were elaborated for the determination of the enantiomeric purity of (R)-MDL 100,907 and its preparatively resolved key intermediate compound during the synthesis route. The pKa values of the intermediate compound and the end product determined by CE were 10.5±0.1 and 9.0±0.1, respectively. The enantiopurity of the intermediate compound can be monitored in fully protonated state by applying 15mM sulfobutylether-β-cyclodextrin at pH 5 when the peak belonging to the impurity migrates before the main component. The fact that the consecutive steps of the synthesis do not affect the enantiomeric purity was verified by the other, newly developed CE method. The enantiomers of rac-MDL 100,907 were resolved by 15mM carboxymethyl-γ-cyclodextrin at pH 3. The applicability (selectivity, LOD, LOQ, repeatability, precision and accuracy) of the methods was studied as well.
Institute of Molecular Pharmacology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, P.O.B.: 17, H-1525 Budapest, Hungary. Electronic address: nemeth.krisztina@ttk.mta.hu.
Krisztina
K
Németh
Roberta
R
Palkó
Péter
P
Kovács
Júlia
J
Visy
D019075:Electrophoresis, Capillary / Q000379:methods*; D005464:Fluorobenzenes / Q000032:analysis* / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D010880:Piperidines / Q000032:analysis* / Q000737:chemistry; D011522:Protons; D044402:Receptor, Serotonin, 5-HT2A / Q000737:chemistry*; D015203:Reproducibility of Results; D012702:Serotonin Antagonists / Q000032:analysis* / Q000737:chemistry; D013237:Stereoisomerism; D047392:beta-Cyclodextrins / Q000737:chemistry; D047408:gamma-Cyclodextrins / Q000737:chemistry
D005464:Fluorobenzenes; D010880:Piperidines; D011522:Protons; D044402:Receptor, Serotonin, 5-HT2A; D012702:Serotonin Antagonists; D047392:beta-Cyclodextrins; C092583:carboxymethyl-gamma-cyclodextrin; D047408:gamma-Cyclodextrins; C093196:SBE4-beta-cyclodextrin; C079049:volinanserin; C031215:betadex
Chiral capillary electrophoresis; Complex stability constant; Enantiomer purity; Negatively charged cyclodextrin derivative; Serotonin receptor antagonist