A chiral separation strategy for acidic drugs in capillary electrochromatography using both chlorinated and nonchlorinated polysaccharide-based selectors.

A generic chiral separation strategy for the analysis of acidic compounds in CEC is proposed in completion of an earlier defined strategy for nonacidic compounds. The screening step of this strategy uses a 45 mM ammonium formate (pH 2.9)/ACN (35/65, v/v) mobile phase, a temperature of 25°C, and an applied voltage of 15 kV. To update the screening step, eight chiral stationary phases, which all possessed chlorinated and nonchlorinated polysaccharide-based chiral selectors, were evaluated using the earlier defined screening conditions. A combination of the two types of polysaccharide-based chiral phases proved to have the highest cumulative success rate. In the updated screening step, amylose tris(3,5-dimethylphenylcarbamate) (ADH), cellulose tris(4-methylbenzoate) (OJH), cellulose tris(3,5-dichlorophenylcarbamate) (SP5), and cellulose tris(3,5-dimethylphenylcarbamate) (ODRH) were included as selectors and their preferred screening sequence was determined as ADH > OJH > SP5 > ODRH. New optimization steps were also defined for SP5 by investigating the influences of different parameters on the separation outcome using an experimental design approach. After application of the updated strategy, 15 of 17 acidic pharmaceuticals were separated under screening conditions, of which 9 were baseline resolved. When the optimization steps were applied, another three compounds were baseline separated, while the total number of separations was increased by one, which brings the total number of separations to 16 of 17 with 12 baseline separated compounds. This reflects the successful performance of the updated strategy on acidic compounds.

Updating a chiral separation strategy for non-acidic drugs with capillary electrochromatography applicable for both chlorinated and non-chlorinated polysaccharide selectors.

A generic strategy for the chiral separation of non-acidic pharmaceuticals was updated to complete an approach defined earlier. The selected chiral stationary phases are all polysaccharide selectors, chlorinated, and non-chlorinated, namely Lux(®) Amylose 2, Chiralcel(®) OD-RH, Lux(®) Cellulose 4, and Chiralpak(®) AD-RH. In this study, the screening step of a strategy defined earlier was updated and the optimization steps were re-evaluated for the applied chiral stationary phases. These screening and optimization conditions were studied by analyzing 20 pharmaceuticals at different organic modifier contents, temperatures, or applied voltages. The proposed chiral separation strategy was then evaluated with a test set of 19 non-acidic drugs. Seventeen compounds (89.5%) of the latter set could be resolved of which eight (42%) were baseline separated. The strategy thus proved to be applicable on compounds different from those used for its development.

Comparative enantioseparations of pharmaceuticals in capillary electrochromatography on polysaccharide-based chiral stationary phases containing selectors with or without chlorinated derivatives.

The screening conditions of an existing chiral strategy in CEC were tested for their applicability on four chlorine-containing polysaccharide-based stationary phases. The selectors of these phases are cellulose tris(3-chloro-4-methylphenylcarbamate), amylose tris(5-chloro-2-methylphenylcarbamate), cellulose tris(4-chloro-3-methylphenylcarbamate) and cellulose tris(3,5-dichlorophenylcarbamate). The enantioselectivity of these phases was compared with those of the four phases without chlorine (Chiralpak® AD-RH, Chiralcel® OD-RH, Chiralpak® AS-RH and Chiralcel® OJ-RH) used in the earlier defined strategy. A test set of 48 structurally diverse drug compounds was analyzed using the screening conditions of the strategy. These results led to possibilities to upgrade the current screening strategy so that improved success rates are obtained. The chlorine-containing chiral stationary phases demonstrated an added value to the screening process since they showed enantioresolution for compounds not resolved by the chiral stationary phases not containing chlorine in their structure.

Monolithic silica capillary columns with immobilized cellulose tris(3,5-dimethylphenylcarbamate) for enantiomer separations in CEC.

Two types of monolithic silica capillary columns with an immobilized cellulose tris(3,5-dimethylphenylcarbamate) (CDMPC) selector were prepared for enantiomer separations in CEC. The monolithic columns were prepared by a sol-gel process in fused-silica capillaries. CDMPC was then either immobilized on a silica monolith through an intermolecular polycondensation of the cellulose derivative containing a triethoxysilyl group, or on a vinylized silica monolith through radical copolymerization of the cellulose derivative, which also contained a vinyl group. IR spectra confirmed the successful immobilization of CDMPC on both columns. Eleven chiral compounds were used to evaluate the enantioselectivity on both column types. Results indicated that the columns obtained via polycondensation had higher separation ability than those obtained via radical polymerization, and that they showed satisfactory run-to-run repeatability and stability. These new techniques thus provide strategies for preparing immobilized polysaccharide-based chiral silica monolithic capillary columns for chiral separations by means of CEC.