Computer simulation of the enantioselective separation of weak bases in an online capillary electrophoresis based microanalysis configuration comprising sulfated cyclodextrin as selector

Abstract

Computer simulation was utilized to characterize the electrophoretic processes occurring after reactant mixing in an online assay format used for monitoring the enantioselective N-demethylation of ketamine to norketamine in the presence of highly sulfated γ-cyclodextrin (HS-γ-CD). The incubated reaction mixture (at pH 7.4 and without chiral selector) is bracketed by a low pH BGE containing 2% HS-γ-CD as chiral selector, thereby forming a discontinuous buffer system. Upon power application, simulation provides insight into the formation of moving boundaries and new zones together with the prediction of the behavior of ketamine and norketamine enantiomers. The analytes first migrate cationically in a zone electrophoretic manner until they come in contact with HS-γ-CD upon which enantioseparation is initiated. Complexation has a focusing effect and the electrophoretic transport becomes reversed, that is, toward the anode. Simulation revealed that the initial conditions for the chiral separation, including buffer components concentrations, pH, and ionic strength, are different than those in the BGE. As a consequence thereof, the experimentally determined complexation parameters for the BGE were unable to correctly describe the migration behavior of the analytes in this column section. An increase in the input binding constants by a factor of two to four, as a result of the decreased ionic strength, resulted in simulation data that agreed with experimental findings.

Inverse cationic ITP for separation of methadone enantiomers with sulfated β‐cyclodextrin as chiral selector

“…Furthermore, in discontinuous buffer systems properties affecting complexation, including the ionic strength, vary along the separation column (Fig. and ) and the impact of ionic strength on complexation is not considered by the simulator used in our work. The influence of the complexation parameters on the methadone zone formation was investigated by simulation using different input values for complexation.…”

“…with an apparent complexation constant K and a mobility of the formed complex u c (Table 1). This approach was successfully used previously in our work with S-␤-CD and the enantiomers of methadone [18], ketamine [29] and norketamine [29]. In this work methadone enantiomer separations were effected with S-␤-CD lot 03711JA, a multiple isomer S-␤-CD with 7-11 sulfated groups per CD.…”

Bioanalysis of drugs and their metabolites by chiral electromigration techniques (2010–2020)

“…The conductivity of the incubation mixture is much higher compared to the conductivity of the BGE. Simulation efforts provided insight into the diffusional mixing of the reactants and buffer constituents [61] and, upon power application, into the formation of moving boundaries and new zones [61,101]. In this…”

“…In this system, the analytes first migrate cationically in a zone electrophoretic manner until they come in contact with the negatively charged chiral selector. Complexation of the analytes has a focusing effect, reverses the electrophoretic transport of the analytes and enables enantioseparation [101].…”

Contemporary chiral simulators for capillary zone electrophoresis

“…SIMUL5complex was used to elucidate the impact of the complexation of buffer constituents with neutral agents on common buffer properties and analyte and system peaks in CZE , and to provide insight into the sweeping process of a drug in presence of a neutral CD . Furthermore, the fundamentals of field‐amplified electrokinetic injection of cations for enantioselective CZE with sulfated β‐cyclodextrin (S‐β‐CD) , the characterization of isomer mixtures of S‐β‐CD , the investigation of the enantioselective separation of weak bases in an on‐line CZE microanalysis configuration comprising S‐β‐CD as selector , and the exploration of inverse cationic ITP for separation of methadone enantiomers with S‐β‐CD as chiral selector were also studied with this simulator. The MEKC behavior of neutral analytes in presence of SDS and the comparison of transient trapping with sweeping in MEKC with SDS were investigated with GENTRANS.…”