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.

Chiral separations of cathinone and amphetamine-derivatives: Comparative study between capillary electrochromatography, supercritical fluid chromatography and three liquid chromatographic modes.

The screening part of an earlier defined chiral separation strategy in capillary electrochromatography (CEC) was used for the separation of ten cathinone- and amphetamine derivatives. They were analyzed using 4 polysaccharide-based chiral stationary phases (CSPs), containing cellulose tris(3,5-dimethylphenylcarbamate) (ODRH), amylose tris(3,5-dimethylphenylcarbamate) (ADH), amylose tris(5-chloro-2-methylphenylcarbamate) (LA2), and cellulose tris(4-chloro-3-methylphenylcarbamate) (LC4) as chiral selectors. After applying the screening to each compound, ADH and LC4 showed the highest success rate. In a second part of the study, a comparison between CEC and other analytical techniques used for chiral separations i.e., supercritical fluid chromatography (SFC), polar organic solvent chromatography (POSC), reversed-phase (RPLC) and normal-phase liquid chromatography (NPLC), was made. For this purpose, earlier defined screening approaches for each technique were applied to separate the 10 test substances. This allowed an overall comparison of the success rates of the screening steps of the 5 techniques for these compounds. The results showed that CEC had a similar enantioselectivity rate as NPLC and RPLC, producing the highest number of separations (9 out of 10 racemates). SFC resolved 7 compounds, while POSC gave only 2 separations. On the other hand, the baseline separation success rates for NPLC and RPLC was better than for CEC. For a second comparison, the same chiral stationary phases as in the CEC screening were also tested with all techniques at their specific screening conditions, which allowed a direct comparison of the performance of CEC versus the same CSPs in the other techniques. This comparison revealed that RPLC was able to separate all tested compounds, and also produced the highest number of baseline separations on the CSP that were used in the CEC screening step. CEC and NPLC showed the same success rate: nine out of ten substances were separated. When CEC and NPLC are combined, separation of the ten compounds can be achieved. SFC and POSC resolved eight and three compounds, respectively. POSC was the least attractive option as it expressed only limited enantioselectivity toward these compounds.