Evaluation of three neutral capillary coatings for the determination of analyte-cyclodextrin binding constants by affinity capillary electrophoresis. Application to N,N'-disubstituted piperazine derivatives.
The performances of three neutral static coatings (hydroxypropyl cellulose, polyethylene oxide and poly(N,N-dimethylacrylamide) have been evaluated in order to determine the binding constants of the complexes formed between four polycationic compounds (piperazine derivatives) and four cyclodextrins of pharmaceutical interest (β-CD, HP-β-CD, Me-β-CD and sulfobutyl ether-β-CD) by affinity capillary electrophoresis. The physically-adsorbed poly(N,N-dimethylacrylamide) coating proves to be the more efficient to mask the silanol groups of the capillary wall since the lowest electroosmotic flow was measured for this coating. Moreover, it drastically reduces the adsorption of the compounds since it allows a correct repeatability of their migration time, higher efficiencies of the peaks and no baseline shift. Then, it was verified for four complexes that this coating allows a correct determination of the binding constants avoiding the CD adsorption which is responsible of an undervaluation of binding constants. The highest binding constants are obtained using the anionic sulfobutyl ether-β-CD (SBE-β-CD). The structure of the complex formed between the tacrine derivative and the SBE-β-CD was further investigated through 2D ROESY NMR experiments and structure-binding constant relationships. Results suggest that the inclusion in the SBE-β-CD cavity occurs through the aliphatic ring portion of the tacrine moiety.
Univ. Lille, CHU Lille, EA 7365 ⿿ GRITA ⿿ Groupe de Recherche sur les formes Injectables et les Technologies Associées, F-59000 Lille, France. Electronic address: cecile.danel@univ-lille2.fr.
Cécile
C
Danel
Univ. Lille, Inserm, CHU Lille, UMR-S 1172 ⿿ JPArc ⿿ Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, F-59000 Lille, France. Electronic address: patricia.melnyk@univ-lille2.fr.
Patricia
P
Melnyk
Univ. Lille, CHU Lille, EA 7365 ⿿ GRITA ⿿ Groupe de Recherche sur les formes Injectables et les Technologies Associées, F-59000 Lille, France. Electronic address: nathalie.azaroual@univ-lille2.fr.
Nathalie
N
Azaroual
Univ. Lille, Inserm, CHU Lille, UMR-S 1172 ⿿ JPArc ⿿ Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, F-59000 Lille, France. Electronic address: paul-emmanuel.larchanche@univ-lille2.fr.
Paul-Emmanuel
PE
Larchanché
Univ. Lille, CHU Lille, EA 7365 ⿿ GRITA ⿿ Groupe de Recherche sur les formes Injectables et les Technologies Associées, F-59000 Lille, France. Electronic address: jean-francois.goossens@univ-lille2.fr.
Jean-François
JF
Goossens
Univ. Lille, CHU Lille, EA 7365 ⿿ GRITA ⿿ Groupe de Recherche sur les formes Injectables et les Technologies Associées, F-59000 Lille, France. Electronic address: claude.vaccher@univ-lille2.fr.
Claude
C
Vaccher
D000178:Acrylamides / Q000737:chemistry; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D003505:Cyclodextrins / Q000737:chemistry*; D019075:Electrophoresis, Capillary; D009682:Magnetic Resonance Spectroscopy; D010879:Piperazines / Q000737:chemistry* / Q000302:isolation & purification; D011092:Polyethylene Glycols / Q000737:chemistry; D014783:Viscosity
D000178:Acrylamides; D003505:Cyclodextrins; D010879:Piperazines; C429790:poly(N,N-dimethylacrylamide); D011092:Polyethylene Glycols; D002482:Cellulose; C008079:hydroxypropylcellulose
Affinity capillary electrophoresis; Cyclodextrin; Hydroxypropyl cellulose; Neutral coating; Poly(N,N-dimethylacrylamide); Polyethylene oxide