Optimization of the enantioseparation of a diaryl‐pyrazole sulfonamide derivative by capillary electrophoresis in a dual CD mode using experimental design

Abstract

A CE method using dual cationic and neutral cyclodextrins (CD) was optimized for the enantiomeric separation of a compound presenting a diaryl sulfonamide group. Preliminary studies were made to select the optimal CDs and pH of the BGE. Two CDs (amino-β-CD and β-CD) were selected to separate the enantiomers in a 67 mM phosphate buffer at pH 7.4. However, the repeatability of the analyses obtained on bare-fused silica capillary was not acceptable owing to the adsorption of the amino-β-CD to the capillary. To prevent this, a dynamic coating of the capillary was used employing five layers of ionic-polymer (poly(diallyldimethylammonium) chloride (PDADMAC) and poly(sodium 4-styrenesulfonate). The efficiency of the coating was assessed by measuring the EOF stability. Repeatability of the injections was obtained when intermediate coating with PDADMAC was performed between each run. Secondly, this enantioseparation method was optimized using a central composite circumscribed design including three factors: amino-β-CD and β-CD concentrations and the percentage of methanol. Under the optimal conditions (i.e. 16.6 mM of amino-β-CD, 2.6 mM of β-CD, 0% MeOH in 67 mM phosphate buffer (pH 7.4) as BGE, cathodic injection 0.5 psi, 5 s, separation voltage 15 kV and a temperature of 15°C), complete enantioresolution of the analyte was obtained. It is worth mentioning that the design of experiments (DOE) protocol employed showed a significant interaction between CDs, highlighting the utility of DOE in method development. Finally, small variations in the ionic-polymer concentrations did not significantly influence the EOF, confirming the robustness of the coating method.

Application of Experimental Design Methodologies in the Enantioseparation of Pharmaceuticals by Capillary Electrophoresis: A Review

“…The method was optimized using a CCC design with three experimental factors: amino-β-CD and β-CD concentrations and methanol percentage in the BGE. The design results showed a significant interaction effect of the two CDs on chiral resolution [ 86 ].…”

Recent development of cationic cyclodextrins for chiral separation

“…Rogez-Florent et al [34] established a CE method using a dual system containing AMCD and native CD for enantioseparation of a diaryl-pyrazole sulfonamide derivative. By employing five layers of ionic poly(diallyldimethylammonium) chloride and poly(sodium 4-styrenesulfonate) as a dynamic coating inside the capillary, the adsorption of AMCD was effectively prevented to enable the repeatability of EOF between each run.…”

“…The repeatability of EOF between each run was therefore achieved by effectively suppressing the adsorption of AMCD on the capillary wall by using multilayers of ionic poly(diallyldimethylammonium) chloride and poly(sodium 4-styrenesulfonate) as the dynamic coating [34]. For NACE, the ammonium camphorsulfonate was added into methanol to restrain the adsorption of cationic CD onto the capillary wall and to avoid the loss of peak efficiency [37].…”

Recent trends in capillary electrophoresis for complex samples analysis: A review

“…However, cationic cyclodextrin have a tendency to adsorb in the uncoated capillary inner walls. This behavior was avoid by using a multiple‐layer dynamic coating based on the addition of cationic poly(diallyldimethylammonium) chloride and anionic poly(sodium 4‐styrenesulfonate) . Then, a five‐layer polymeric coating was formed (cationic external layer), allowing the chiral separation of diaryl‐pyrazole sulfonamide derivative using a mixture of amino‐β‐CD and β‐CD as chiral selectors.…”