Generic systems for the enantioseparation of basic drugs in NACE using single-isomer anionic CDs.
The enantioseparation of 10 basic drugs was evaluated in NACE systems using heptakis(2-O-methyl-3-O-acetyl-6-O-sulfo)-β-CD (HMAS-β-CD). For this purpose, a D-optimal design with 21 experimental points was applied. Four antifungal agents (econazole, isoconazole, miconazole, sulconazole), three local anesthetics (bupivacaine, mepivacaine and prilocaine), two sympathomimetics (salbutamol and terbutaline) and one β-blocker (carvedilol) were selected as basic model analytes. The influence on the enantiomeric resolution of anionic CD and BGE anion concentrations as well as the BGE anion nature was investigated. For all studied analytes, the enantiomeric resolution was shown to be significantly influenced by the CD concentration. Based on the observed results, a generic NACE system was recommended, namely 20mM HMAS-β-CD and 10mM ammonium camphor SO(3)(-) in methanol acidified with 0.75 M formic acid. Moreover, this NACE system was compared to previous conditions with heptakis(2,3-di-O-methyl-6-O-sulfo)-β-CD (HDMS-β-CD) or heptakis(2,3-di-O-acetyl-6-O-sulfo)-β-CD (HDAS-β-CD). Finally, two generic systems using either HDAS-β-CD or HMAS-β-CD were proposed and evaluated for the enantioseparation of ketamine and norketamine after incubation of ketamine in phenobarbital-induced male rat liver microsomes systems.
Rousseau
Anne
A
Department of Analytical Pharmaceutical Chemistry, Institute of Pharmacy, University of Liège, CHU, B36, B-4000 Liège 1, Belgium.
Gillotin
Florian
F
Chiap
Patrice
P
Bodoki
Ede
E
Crommen
Jacques
J
Fillet
Marianne
M
Servais
Anne-Catherine
AC
D000818:Animals; D000838:Anions; D000935:Antifungal Agents / Q000737:chemistry*; D015195:Drug Design; D004586:Electrophoresis / Q000379:methods; D019075:Electrophoresis, Capillary / Q000379:methods*; D007649:Ketamine / Q000031:analogs & derivatives / Q000737:chemistry; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D008956:Models, Chemical; D051381:Rats; D013237:Stereoisomerism; D013997:Time Factors; D047392:beta-Cyclodextrins / Q000737:chemistry*
D000838:Anions; D000935:Antifungal Agents; D047392:beta-Cyclodextrins; D007649:Ketamine; C033419:norketamine