Application of capillary electrophoresis for high-throughput
screening of drug metabolism

C 2013

Application of capillary electrophoresis for high-throughput screening of drug metabolism

ŘEMÍNEK, Roman, Jochen PAUWELS, Xu WANG, Jos HOOGMARTENS, Zdeněk GLATZ et. al.

Basic information

Original name

Application of capillary electrophoresis for high-throughput screening of drug metabolism

Name in Czech

Využití kapilární elektroforézy pro testování metabolismu léčiv

Authors

ŘEMÍNEK, Roman (203 Czech Republic, belonging to the institution), Jochen PAUWELS (56 Belgium), Xu WANG (156 China), Jos HOOGMARTENS (56 Belgium), Zdeněk GLATZ (203 Czech Republic, guarantor, belonging to the institution) and Ann VAN SCHEPDAEL (56 Belgium)

Edition

1. vyd. Hoboken, New Jersey, Capillary Electrophoresis and Microchip Capillary Electrophoresis: Principles, Applications, and Limitations, p. 309-317, 9 pp. 2013

Publisher

John Wiley & Sons, Inc.

Other information

Language

English

Type of outcome

Kapitola resp. kapitoly v odborné knize

Field of Study

10600 1.6 Biological sciences

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

Publication form

printed version "print"

References:

URL

RIV identification code

RIV/00216224:14310/13:00066018

Organization unit

Faculty of Science

ISBN

978-0-470-57217-7

DOI

http://dx.doi.org/10.1002/9781118530009.ch17

Keywords (in Czech)

kapilární elektroforéza; lidské jaterní mikrosomy; cytochromy P450; vývoj léčiv; stabilita léčiv;

Keywords in English

Capillary electrophoresis; human liver microsomes; cytochrome P450 enzyme; drug development; metabolic stability;

Abstract

ORIG CZ

V originále

Pharmaceutical industry currently needs to screen extensive compound libraries within pre-clinical stages of drug development. Capillary electrophoresis has become a well-established analytical technique during the last two decades. In spite of the fact that capillary electrophoresis offers a number of favorable features for high-throughput analytical assays, it is still less important than chromatographic techniques in drug development programs. Hence, the main aim of this chapter is to discuss the practical limitations of capillary electrophoresis utilization and suggest ways to overcome these constraints. This is illustrated with a practical example namely the introduction of a method allowing rapid characterization of a compound’s stability against human liver microsomes. NADP+ production monitoring was adopted to ensure generic applicability of the method. The fast stability screening of 12 chosen probe drugs and determination of apparent kinetic parameters for the lidocaine/human liver microsomes system were performed in order to demonstrate the potential of the final method. The results were in a good agreement with the literature data determined by different methods.

In Czech

Byla zavedena metoda pro rychlé stanovení stability léčiv vůči mikrosomálním enzymům. Možnosti metody byly demonstrovány na screeningu 12 vybraných substrátů.

Links

EE2.3.20.0182, research and development project

Name: Vytvoření multidisciplinárního výzkumného a vzdělávacího centra bioanalytických technologií

GAP206/10/0057, research and development project

Name: Miniaturizovaný systém pro "on-line" studie metabolismu léčiv založený na kapilární elektroforéze

Investor: Czech Science Foundation, Miniaturized on-line drug metabolism system based on capillary electrophoresis

Citovat

ŘEMÍNEK, Roman, Jochen PAUWELS, Xu WANG, Jos HOOGMARTENS, Zdeněk GLATZ and Ann VAN SCHEPDAEL. Application of capillary electrophoresis for high-throughput screening of drug metabolism. In Carlos D. García, Karin Y. Chumbimuni-Torres, Emanuel Carrilho. Capillary Electrophoresis and Microchip Capillary Electrophoresis: Principles, Applications, and Limitations. 1st ed. Hoboken, New Jersey: John Wiley & Sons, Inc., 2013, p. 309-317. ISBN 978-0-470-57217-7. Available from: https://dx.doi.org/10.1002/9781118530009.ch17.

@inbook{1088283,
   author = {Řemínek, Roman and Pauwels, Jochen and Wang, Xu and Hoogmartens, Jos and Glatz, Zdeněk and Van Schepdael, Ann},
   address = {Hoboken, New Jersey},
   booktitle = {Capillary Electrophoresis and Microchip Capillary Electrophoresis: Principles, Applications, and Limitations},
   doi = {http://dx.doi.org/10.1002/9781118530009.ch17},
   edition = {1.},
   editor = {Carlos D. García, Karin Y. Chumbimuni-Torres, Emanuel Carrilho},
   keywords = {Capillary electrophoresis; human liver microsomes; cytochrome P450 enzyme; drug development; metabolic stability;},
   howpublished = {tištěná verze "print"},
   language = {eng},
   location = {Hoboken, New Jersey},
   isbn = {978-0-470-57217-7},
   pages = {309-317},
   publisher = {John Wiley & Sons, Inc.},
   title = {Application of capillary electrophoresis for high-throughput screening of drug metabolism},
   url = {http://eu.wiley.com/WileyCDA/WileyTitle/productCd-0470572175,descCd-description.html},
   year = {2013}
}

TY  - CHAP
ID  - 1088283
AU  - Řemínek, Roman - Pauwels, Jochen - Wang, Xu - Hoogmartens, Jos - Glatz, Zdeněk - Van Schepdael, Ann
PY  - 2013
TI  - Application of capillary electrophoresis for high-throughput screening of drug metabolism
VL  - Neuveden
PB  - John Wiley & Sons, Inc.
CY  - Hoboken, New Jersey
SN  - 9780470572177
KW  - Capillary electrophoresis
KW  - human liver microsomes
KW  - cytochrome P450 enzyme
KW  - drug development
KW  - metabolic stability;
UR  - http://eu.wiley.com/WileyCDA/WileyTitle/productCd-0470572175,descCd-description.html
N2  - Pharmaceutical industry currently needs to screen extensive compound libraries within pre-clinical stages of drug development. Capillary electrophoresis has become a well-established analytical technique during the last two decades. In spite of the fact that capillary electrophoresis offers a number of favorable features for high-throughput analytical assays, it is still less important than chromatographic techniques in drug development programs. Hence, the main aim of this chapter is to discuss the practical limitations of capillary electrophoresis utilization and suggest ways to overcome these constraints. This is illustrated with a practical example namely the introduction of a method allowing rapid characterization of a compound’s stability against human liver microsomes. NADP+ production monitoring was adopted to ensure generic applicability of the method. The fast stability screening of 12 chosen probe drugs and determination of apparent kinetic parameters for the lidocaine/human liver microsomes system were performed in order to demonstrate the potential of the final method. The results were in a good agreement with the literature data determined by different methods.
ER  -

ŘEMÍNEK, Roman, Jochen PAUWELS, Xu WANG, Jos HOOGMARTENS, Zdeněk GLATZ and Ann VAN SCHEPDAEL. Application of capillary electrophoresis for high-throughput screening of drug metabolism. In Carlos D. García, Karin Y. Chumbimuni-Torres, Emanuel Carrilho. \textit{Capillary Electrophoresis and Microchip Capillary Electrophoresis: Principles, Applications, and Limitations}. 1st ed. Hoboken, New Jersey: John Wiley \&{} Sons, Inc., 2013, p.~309-317. ISBN~978-0-470-57217-7. Available from: https://dx.doi.org/10.1002/9781118530009.ch17.

Detailed Information on Publication Record