Toward an automated workflow for the study of plasma protein-drug interactions based on capillary electrophoresis-frontal analysis combined with in-capillary mixing of interacting partners

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F21%3A00118782" target="_blank" >RIV/00216224:14310/21:00118782 - isvavai.cz</a>

Result on the web

<a href="https://doi.org/10.1016/j.chroma.2020.461734" target="_blank" >https://doi.org/10.1016/j.chroma.2020.461734</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.chroma.2020.461734" target="_blank" >10.1016/j.chroma.2020.461734</a>

Result language

angličtina

Original language name

Toward an automated workflow for the study of plasma protein-drug interactions based on capillary electrophoresis-frontal analysis combined with in-capillary mixing of interacting partners

Original language description

Capillary electrophoresis-frontal analysis (CE-FA) together with mobility shift affinity CE is the most frequently used mode of affinity CE for a study of plasma protein-drug interactions, which is a substantial part of the early stage of drug discovery. Whereas in the classic CE-FA setup the sample is prepared by off-line mixing of the interaction partners in the sample vial outside the CE instrument and after a short incubation period loaded into the capillary and analysed, in this work a new methodological approach has been developed that combines CE-FA with the mixing of interacting partners directly inside the capillary. This combination gives rise to a fully automated and versatile methodology for the characterization of these binding interactions besides a substantial reduction in the amounts of sample compounds used. The minimization of possible experimental errors due to the full involving of sophisticated CE instrument in the injection procedure, mixing and separation instead of manual manipulation is another fundamental benefit. The in-capillary mixing is based on the transverse diffusion of laminar flow profile methodology introduced by Krylov et al. using its multi-zone injection modification presented by Řemínek at al.. Actually, after the method optimization, the alternate introduction of six plugs of drug and six plugs of bovine serum protein in BGE, each injected for 3 s at a pressure of -10 mbar (-1 kPa) into the capillary filled by BGE, was found to be the best injection procedure. The method repeatability calculated as RSDs of plateau highs of bovine serum albumin and propranolol as model sample compounds were better than 3.44 %. Its applicability was finally demonstrated on the determination of apparent binding parameters of bovine serum albumin for basic drugs propranolol and lidocaine and acid drug phenylbutazone. The values obtained by a new on-line CE-FA methodology are in agreement with values estimated by classic off-line CE-FA, as well as with literature data obtained using different techniques.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10600 - Biological sciences

Project

<a href="/en/project/GA19-08358S" target="_blank" >GA19-08358S: New approaches for the study of affinity interaction based on capillary electrophoresis</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2021

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Chromatography A

ISSN

0021-9673

e-ISSN

1873-3778

Volume of the periodical

1635

Issue of the periodical within the volume

January 2021

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

9

Pages from-to

461734

UT code for WoS article

000603564600006

EID of the result in the Scopus database

2-s2.0-85096881675