Strategy for the chiral separation of non-acidic pharmaceuticals using capillary electrochromatography.
In completion of an earlier defined generic chiral screening approach, a generic separation strategy for basic, bifunctional, and neutral compounds was proposed and evaluated. This strategy adds to a previously defined strategy for acidic compounds. The screening experiment of the actual strategy used a mobile phase of 5 mM phosphate buffer pH 11.5/ACN (30/70 v/v), a temperature of 25 degrees C, and a voltage of 15 kV. The selected chiral stationary phases were Chiralpak AD-RH, Chiralcel OD-RH, Chiralcel OJ-RH, and Chiralpak AS-RH, all based on polysaccharide selectors. It was seen that 31 out of 48 test compounds were partially or baseline-resolved under screening conditions. After execution of the optimization steps of the strategy, this number increased to 41, with a total of 21 baseline-separated compounds. Combined with the results obtained from the acidic test set examined in the earlier defined strategy, of all tested compounds 82.5% showed enantioselectivity and 49.2% could be baseline-separated.
Mangelings
Debby
D
Department of Pharmaceutical and Biomedical Analysis, Pharmaceutical Institute, Vrije Universiteit Brussel-VUB, Brussels, Belgium.
Discry
Jérôme
J
Maftouh
Mohamed
M
Massart
D Luc
DL
Vander Heyden
Yvan
Y
D000688:Amylose / Q000031:analogs & derivatives; D002021:Buffers; D002482:Cellulose / Q000031:analogs & derivatives; D019075:Electrophoresis, Capillary / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000302:isolation & purification*; D048448:Phenylcarbamates; D055672:Static Electricity; D013237:Stereoisomerism; D013696:Temperature
D002021:Buffers; D004364:Pharmaceutical Preparations; D048448:Phenylcarbamates; C065943:cellulose tris-3,5-dimethylphenyl-carbamate; C080033:Chiralpak AD; D002482:Cellulose; D000688:Amylose