Evaluation of the enantioselective binding of imazalil to human serum albumin by capillary electrophoresis

Abstract

In this work, a methodology for the evaluation of enantioselective binding of imazalil (IMA) enantiomers to human serum albumin (HSA) that does not require the separation of free and bound to HSA fractions is developed. This methodology comprises the incubation of IMA-HSA designed mixtures for 30 min directly in the capillary electrophoresis system and the subsequent direct injection and chiral separation of IMA employing highly sulfated β-cyclodextrin as chiral selector and the complete filling technique. Two mathematical approaches were used to estimate apparent affinity constants (K1), protein binding and enantioselectivity (ES) for both enantiomers of IMA. Moderate enantioselective binding of IMA enantiomers to HSA (ES = 2.0) was shown by the 1:1 stoichiometry and log K1 values of 3.4 ± 0.4 and 3.1 ± 0.3 for the first and second eluted enantiomers, respectively.

Chiral selectors in CE: Recent development and applications (mid‐2014 to mid‐2016)

“…A new and simple methodology for the evaluation of the enantioselective binding of imazalil to human serum albumin was developed in CE by using HS‐β‐CD . A satisfactory separation of imazalil enantiomers was achieved ( R S = 4.4) in less than 6.5 min, and, as stated by the authors, this was the first evidence of toxicokinetic data for imazalil.…”

“…In contrast to the conventional approaches, in this study, the preincubation of imazalil‐albumin mixtures and their direct injection in CE without the use of membrane‐based separation techniques avoided the nonspecific adsorption of the xenobiotic to the filtration or dialysis devices, while the cost and analysis time were reduced. The same research group characterized the interaction between the enantiomers of eight psychoactive drugs and HS‐β‐CD by use of countercurrent CE . The enantiomers of four antihistamines (dimethindene, promethazine, orphenadrine, and terfenadine) and four antidepressants (bupropion, fluoxetine, nomifensine, and viloxazine) were separated, for the first time, by the use of this particular CD.…”

“…Other experimental conditions are as follows: BGE, 30 mM phosphate buffer, pH 7.0; applied voltage, 15 kV. Reprinted with permission from .…”

Fast evaluation of enantioselective drug metabolism by electrophoretically mediated microanalysis: Application to fluoxetine metabolism by CYP2D6

“…Initial conditions for the electrophoretic separation (BGE, 50 mM NaH 2 PO 4 at pH 8.8; capillary temperature, 25°C, separation voltage, 20 kV + 0.2 psi of pressure; HS‐β‐CD 2.5% w/v injected at 20 psi/2 min) were taken from . However, based on our previous experience about the chiral separation of FLX with HS‐β‐CD, the CD concentration used there (2.5% w/v) was considered too high due to the strong interaction between the FLX enantiomers and the HS‐β‐CD . Therefore, a study was performed in order to select the adequate CD concentration, which allows the separation of all components of the enzymatic reaction.…”

Enantioselective simultaneous analysis of selected pharmaceuticals in environmental samples by ultrahigh performance supercritical fluid based chromatography tandem mass spectrometry

“…Imazalil is employed as a racemic mixture and the general population can be exposed to it through contaminated food. A previous study has shown that the binding of imazalil to human proteins, specifically human serum albumin, is enantioselective [32], what could suggest that imazalil is excreted with an excess of one enantiomer or that chiral inversion took place, but this effect has been scarcely studied so there is not enough information available regarding this effect. Moreover, recent published data showed that the S-(À)-enantiomer degrades quicker than the R-(þ)-enantiomer [33,34], what could explain the presence of only one enantiomer in influent wastewater samples.…”