Dynamic high‐resolution computer simulation of isotachophoretic enantiomer separation and zone stability

Abstract

The development of electrophoretic computer models and their use for simulation of electrophoretic processes has increased significantly during the last few years. Recently, GENTRANS and SIMUL5 were extended with algorithms that describe chemical equilibria between solutes and a buffer additive in a fast 1:1 interaction process, an approach that enables simulation of the electrophoretic separation of enantiomers. For acidic cationic systems with sodium and H3 0(+) as leading and terminating components, respectively, acetic acid as counter component, charged weak bases as samples, and a neutral CD as chiral selector, the new codes were used to investigate the dynamics of isotachophoretic adjustment of enantiomers, enantiomer separation, boundaries between enantiomers and between an enantiomer and a buffer constituent of like charge, and zone stability. The impact of leader pH, selector concentration, free mobility of the weak base, mobilities of the formed complexes and complexation constants could thereby be elucidated. For selected examples with methadone enantiomers as analytes and (2-hydroxypropyl)-β-CD as selector, simulated zone patterns were found to compare well with those monitored experimentally in capillary setups with two conductivity detectors or an absorbance and a conductivity detector. Simulation represents an elegant way to provide insight into the formation of isotachophoretic boundaries and zone stability in presence of complexation equilibria in a hitherto inaccessible way.

Dynamic computer simulation of electrophoretic enantiomer migration order and separation in presence of a neutral cyclodextrin

“…For the studied example, no migration order inversion is predicted and CEC separations are shown to be quicker and electrophoretic displacement rate reduced in comparison to that in free solution. Dynamic computer simulation also provides insight into analyte stacking across conductivity and buffer additive gradients, changes of additive concentration, buffer component concentration, pH and conductivity across migrating sample zones and peaks, zone dispersion under electrokinetic conditions, and the formation and migration of system peaks as was discussed in previous publications . For example, simulation data revealed that separations of cationic enantiomers in phosphate buffers at low pH occur behind a fast cationic migrating system peak that has a small impact on the buffer composition under which enantiomeric separation takes place .…”

“…Dynamic computer simulation of electrophoretic processes provides component distributions and profiles of the column properties as function of electrophoresis time . The separation of ketoconazole enantiomers in presence of OHP‐β‐CD was first investigated using SIMUL5complex with three concentrations of the chiral selector together with the input data presented in Table (Fig.…”

“…For a given system, separation selectivity can be discussed as functions of CD concentration and pH using algebraic equations . Furthermore, migration behavior in presence of complexation can be studied by dynamic simulation and, for fully charged analytes and a neutral complexation agent, with Peakmaster that comprises a nonlinear model for complex forming systems . These approaches also revealed zone dispersion due to complexation that particularly occurs at low concentration of a chiral selector and high complexation constants .…”

“…They are 1D models with the transport of each component through the electrophoretic space being the result of protolysis, complex formation, electromigration, diffusion, and imposed and/or electrically driven bulk flow. The two models were found to properly describe the dynamics of chiral separations via use of complexation constants and specific mobilities of formed analyte–selector complexes .…”

Computer simulation of electrophoretic aspects of enantiomer migration and separation in capillary electrochromatography with a neutral selector

“…The two models were found to properly describe the migration behavior of enantiomers, dynamics of chiral separations, and formation of system peaks in free solution via use of complexation constants and specific mobilities of analyte–selector complexes . Dynamic simulation revealed zone dispersion due to complexation that can particularly occur at low concentration of a chiral selector and high complexation constants ; migration order reversal that can occur by changing the chiral selector or for a given selector by varying pH of the BGE or, at constant pH, the CD concentration ; occurrence and migration of system peaks ; and isotachophoretic enantiomer separation and zone stability . The same simulators can also be employed to characterize the impact of complexation on the buffer and peak properties in the case of an interaction between the selector and one or several buffer components .…”