Association of two single-isomer anionic CD in NACE for the chiral and achiral separation of fenbendazole, its sulphoxide and sulphone metabolites: application to their determination after in vitro metabolism.
A NACE method was developed for the separation of fenbendazole (FBZ), a prochiral drug giving rise to chiral (oxfendazole or OFZ) and nonchiral (FBZ sulphone or FBZSO(2)) metabolites. First, the effect of the nature and the concentration of CD as well as that of the acidic BGE on the enantiomeric separation of OFZ were studied. OFZ enantiomers were completely resolved using a BGE made up of 10 mM ammonium formate and 0.5 M TFA in methanol containing 10 mM heptakis(2,3-di-O-acetyl-6-O-sulfo)-beta-CD and 10 mM heptakis(2,3-di-O-methyl-6-O-sulfo)-beta-CD. Moreover, the NACE method was found to be particularly well suited to the simultaneous determination of FBZ, OFZ enantiomers, and FBZSO(2). Thiabendazole was selected as an internal standard. The CD-NACE potential was then evaluated for in vitro metabolism studies using FBZ as a model case. The OFZ enantiomers and FBZSO(2) could be detected after incubation of FBZ in the phenobarbital-induced male rat liver microsomes systems.
Rousseau
Anne
A
Department of Analytical Pharmaceutical Chemistry, Institute of Pharmacy, University of Liège, Liège, Belgium.
Gillotin
Florian
F
Chiap
Patrice
P
Crommen
Jacques
J
Fillet
Marianne
M
Servais
Anne-Catherine
AC
D000818:Animals; D001562:Benzimidazoles / Q000737:chemistry* / Q000378:metabolism; D003505:Cyclodextrins / Q000737:chemistry*; D004573:Electrolytes / Q000737:chemistry; D019075:Electrophoresis, Capillary / Q000379:methods*; D005273:Fenbendazole / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D013450:Sulfones / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D013454:Sulfoxides / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D047392:beta-Cyclodextrins / Q000737:chemistry*
D001562:Benzimidazoles; D003505:Cyclodextrins; D004573:Electrolytes; D013450:Sulfones; D013454:Sulfoxides; D047392:beta-Cyclodextrins; C486937:heptakis(2,3-di-O-acetyl-6-O-sulfo)-beta-cyclodextrin; C400661:heptakis(2,3-dimethyl-6-sulfato)cyclodextrin; D005273:Fenbendazole; C011030:oxfendazole