Online Enantioselective Capillary Electrophoretic Method for Screening Cytochrome P450 3A4 Inhibitors.

Řemínek, Roman; Glatz, Zdeněk; Thormann, Wolfgang (2020). Online Enantioselective Capillary Electrophoretic Method for Screening Cytochrome P450 3A4 Inhibitors. In: Labrou, Nikolaos E. (ed.) Targeting Enzymes for Pharmaceutical Development: Methods and Protocols. Methods in Molecular Biology: Vol. 2089 (pp. 167-178). Springer Science+Business Media 10.1007/978-1-0716-0163-1_11

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The market share of single-enantiomer drugs is steadily increasing. The pharmacodynamics and pharmacokinetics of individual enantiomers can differ considerably. Thus, their characteristics have to be addressed as early as possible in the development process of new pharmaceuticals. Capillary electrophoresis is a promising technique for enantioselective drug metabolism studies due to highly effective separations, minuscule consumption of sample and reagents, compatibility with a variety of detection techniques, high-throughput via automation, and the implementation of online procedures. An online method comprised of the diffusion-based mixing of cytochrome P450 3A4 with racemic ketamine, incubation of the enzyme reaction, separation of the reaction products S- and R-norketamine, and their quantification is presented in this chapter. Since diffusion is an inherent property of all molecules, the method enables the addition of virtually any compound to the reaction mixture without the need for additional optimization of the mixing conditions, and thus can be favorably used for the rapid screening of putative cytochrome P450 3A4 inhibitors.

Item Type:

Book Section (Book Chapter)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Laboratory for Clinical Pharmacology

UniBE Contributor:

Thormann, Wolfgang

ISSN:

1940-6029

Series:

Methods in Molecular Biology

Publisher:

Springer Science+Business Media

Language:

English

Submitter:

Wolfgang Thormann

Date Deposited:

04 Dec 2019 10:55

Last Modified:

04 Dec 2019 10:55

Publisher DOI:

10.1007/978-1-0716-0163-1_11

PubMed ID:

31773654

Uncontrolled Keywords:

Capillary electrophoresis Cytochrome P450 3A4 Drug metabolism Enantioselective separation Enzyme inhibition In-capillary reactor Ketamine Transverse diffusion of laminar flow profiles

BORIS DOI:

10.7892/boris.135981

URI:

https://boris.unibe.ch/id/eprint/135981

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