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

Thormann, Wolfgang; Chankvetadze, Lali; Gümüştaş, Mehmet; Chankvetadze, Bezhan

doi:10.1002/elps.201400193

Cited by 22 publications

(23 citation statements)

References 48 publications

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“…In several studies, ACE was combined with other techniques, e.g. NMR spectroscopy , calorimetry and/or computational methods , which allowed to obtain not only stability constant but also other thermodynamic data (Gibbs energy, enthalpy and entropy) of the complexation process and some structural features of the analyzed complexes.…”

Section: Introductionmentioning

confidence: 99%

Estimation of apparent binding constant of complexes of selected acyclic nucleoside phosphonates with β‐cyclodextrin by affinity capillary electrophoresis

et al. 2015

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Affinity capillary electrophoresis (ACE) has been applied to estimation of apparent binding constant of complexes of (R,S)-enantiomers of selected acyclic nucleoside phosphonates (ANPs) with chiral selector β-cyclodextrin (βCD) in aqueous alkaline medium. The noncovalent interactions of five pairs of (R,S)-enantiomers of ANPs-based antiviral drugs and their derivatives with βCD were investigated in the background electrolyte (BGE) composed of 35 or 50 mM sodium tetraborate, pH 10.0, and containing variable concentration (0-25 mM) of βCD. The apparent binding constants of the complexes of (R,S)-enantiomers of ANPs with βCD were estimated from the dependence of effective electrophoretic mobilities of (R,S)-enantiomers of ANPs (measured simultaneously by ACE at constant reference temperature 25°C inside the capillary) on the concentration of βCD in the BGE using different nonlinear and linear calculation methodologies. Nonlinear regression analysis provided more precise and accurate values of the binding constants and a higher correlation coefficient as compared to the regression analysis of the three linearized plots of the effective mobility dependence on βCD concentration in the BGE. The complexes of (R,S)-enantiomers of ANPs with βCD have been found to be relatively weak - their apparent binding constants determined by the nonlinear regression analysis were in the range 13.3-46.4 L/mol whereas the values from the linearized plots spanned the interval 12.3-55.2 L/mol.

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Section: Introductionmentioning

confidence: 99%

Estimation of apparent binding constant of complexes of selected acyclic nucleoside phosphonates with β‐cyclodextrin by affinity capillary electrophoresis

et al. 2015

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“…The separation selectivity A R/S of the R and S enantiomers of a compound is defined as the ratio of the effective mobilities of the two enantiomers and, for a given neutral CD concentration and pH, can be calculated as the product of two factors, the mobility factor A and the selectivity B for zero complex mobility . For the enantiomers of a weak base, separation selectivity can be expressed as:

A_{R / S} = {u_{R}}^{italiceff} / {u_{S}}^{italiceff} = (u_{R} / u_{S}) \times A \times B

with

\begin{matrix} true \\ right A & = & left \frac{(0true 1 + \frac{u_{RCD}}{u_{normalR}} K_{XRc} [CD])}{(0true 1 + \frac{u_{SCD}}{u_{normalS}} K_{XSc} [CD])} and \\ right B & = & left \frac{((), 1 + K_{XSc} [CD] + \frac{K_{HS}}{[{normalH}_{3} O^{+}]} (1 + K_{XSn} [CD]))}{((), 1 + K_{XRc} [CD] + \frac{K_{HR}}{[{normalH}_{3} O^{+}]} (1 + K_{XRn} [CD]))} \end{matrix}

where K HS = K HR is the dissociation constant of the enantiomers S and R , K XSc and K XRc are the complexation constants of the cationic species of the enantiomers S and R , K XSn and K XRn are the complexation constants of the neutral species of the enantiomers S and R , u i eff is the effective mobility of enantiomer i, u i is the ionic mobility of the free enantiomer i (u S = u R ), and u SCD and u RCD are the mobilities of the complexes of the enantiomers with the neutral CD . For the pH 2.50 configuration studied in our work, at which the methadone enantiomers are fully dissociated, the complexation constant of the neutral form does not play an important role.…”

Section: Resultsmentioning

confidence: 99%

“…With immobilization of the chiral selector, the mobilities of the complex and the selector (used to calculate diffusion) become zero. This situation reflects CEC conditions in the absence of nonspecific interactions between solutes and the chiral stationary phase and was briefly discussed for the separation of ketoconazole enantiomers . It provides insights into CEC that are not covered by other CEC modeling efforts .…”

Section: Introductionmentioning

confidence: 98%

“…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 .…”

Section: Introductionmentioning

confidence: 99%

“…For complexation with a neutral CD, separation selectivity can be discussed as functions of CD concentration and pH using algebraic equations . The effective mobility of an enantiomer is a function of the ionic mobilities of the free and complexed forms of the enantiomer, the dissociation constant of the enantiomer, the complex formation constants of ionic and uncharged species of the enantiomer, as well as pH and CD concentration of the BGE.…”

Section: Introductionmentioning

confidence: 99%

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

2015

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A computer simulation study describing the electrophoretic separation and migration of methadone enantiomers in presence of free and immobilized (2-hydroxypropyl)-β-CD is presented. The 1:1 interaction of methadone with the neutral CD was simulated by using experimentally determined mobilities and complexation constants for the complexes in a low-pH BGE comprising phosphoric acid and KOH. The use of complex mobilities represents free solution conditions with the chiral selector being a buffer additive, whereas complex mobilities set to zero provide data that mimic migration and separation with the chiral selector being immobilized, that is CEC conditions in absence of unspecific interaction between analytes and the chiral stationary phase. Simulation data reveal that separations are quicker, electrophoretic displacement rates are reduced, and sensitivity is enhanced in CEC with on-column detection in comparison to free solution conditions. Simulation is used to study electrophoretic analyte behavior at the interface between sample and the CEC column with the chiral selector (analyte stacking) and at the rear end when analytes leave the environment with complexation (analyte destacking). The latter aspect is relevant for off-column analyte detection in CEC and is described here for the first time via the dynamics of migrating analyte zones. Simulation provides insight into means to counteract analyte dilution at the column end via use of a BGE with higher conductivity. Furthermore, the impact of EOF on analyte migration, separation, and detection for configurations with the selector zone being displaced or remaining immobilized under buffer flow is simulated. In all cases, the data reveal that detection should occur within or immediately after the selector zone.

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Simultaneous determination and validation of emtricitabine, rilpivirine and tenofovir from biological samples using LC and CE methods

Gümüştaş

Çağlayan

Onur

et al. 2018

Biomedical Chromatography

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A combination of antiretroviral agents is frequently used in effective treatment of the human immunodeficiency virus infection. In this study, two different separation methods are presented for the simultaneous determination of emtricitabine, rilpivirine and tenofovir from raw materials and urine samples. Developed liquid chromatography and capillary electrophoresis methods were thoroughly optimized for high analytical performances. Optimization of multiple variables at the same time by performing a minimum number of experiments was achieved by the Box-Behnken design, which is an experimental design in response surface methodology, in capillary electrophoresis. The results of the experimental design ensure minimum analysis time with well-separated analytes. Separation conditions, such as different stationary phases, pH level, organic modifiers and temperatures in liquid chromatography method, were also optimized. In particular, among stationary phases, the core-shell column especially enhanced the effectiveness of separation in liquid chromatography. Both methods were fully validated and applied to real samples. The main advantage of the developed methods is the separation of the drug combination in a short time with high efficiency and without any time-consuming steps.

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

Cited by 22 publications

References 48 publications

Estimation of apparent binding constant of complexes of selected acyclic nucleoside phosphonates with β‐cyclodextrin by affinity capillary electrophoresis

Estimation of apparent binding constant of complexes of selected acyclic nucleoside phosphonates with β‐cyclodextrin by affinity capillary electrophoresis

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

Simultaneous determination and validation of emtricitabine, rilpivirine and tenofovir from biological samples using LC and CE methods

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