Investigation of the enantioselective interaction between selected drug enantiomers and human serum albumin by mobility shift-affinity capillary electrophoresis

Ratih, Ratih and Wätzig, Hermann and Stein, Matthias and Deeb, Sami El (2020) Investigation of the enantioselective interaction between selected drug enantiomers and human serum albumin by mobility shift-affinity capillary electrophoresis. Journal of Separation Science. ISSN 1615-9314

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Abstract

Mobility shift-affinity capillary electrophoresis was employed for enantioseparation and simultaneous binding constant determination. Human serum albumin was used as a chiral selector in the background electrolyte composed of 20 mM phosphate buffer, pH 7.4. The applied setup supports a high mobility shift since albumin and the drug-albumin complex hold negative net charges, while model compounds of amlodipine and verapamil are positively charged. In order to have an accurate effective mobility determination, the Haarhoff-van der Linde function was utilized. Subsequently, the association constant was determined by nonlinear regression analysis of the dependence of effective mobilities on the total protein concentration. Differences in the apparent binding status between the enantiomers lead to mobility shifts of different extends (α). This resulted in enantioresolutions of Rs = 1.05–3.63 for both drug models. R-(+)-Verapamil (KA 1844 M−1) proved to bind stronger to human serum albumin compared to S-(−)-verapamil (KA 6.6 M−1). The association constant of S-(−)-amlodipine (KA 25 073 M−1) was found to be slightly higher compared to its antipode (KA 22 620 M−1) when applying the racemic mixture. The low measurement uncertainty of this approach was demonstrated by the close agreement of the association constant of the enantiopure S-(−)-form (KA 25 101 M−1).

Item Type:	Article
Uncontrolled Keywords:	affinity capillary electrophoresis, amlodipine, enantioselective interaction, human serum albumin, mobility-shift assay
Subjects:	R Medicine > RS Pharmacy and materia medica
Divisions:	Faculty of Pharmacy > Department of Pharmacy
Depositing User:	Ester Sri W. 196039
Date Deposited:	02 Feb 2021 02:50
Last Modified:	29 Sep 2023 09:18
URI:	http://repository.ubaya.ac.id/id/eprint/38819

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