Determination of drug stability against human liver microsomes
by utilization of short-end injection capillary electrophoresis
mode

D 2010

Determination of drug stability against human liver microsomes by utilization of short-end injection capillary electrophoresis mode

ŘEMÍNEK, Roman, Jochen PAUWELS, Jos HOOGMARTENS, Ann VAN SCHEPDAEL, Zdeněk GLATZ et. al.

Basic information

Original name

Determination of drug stability against human liver microsomes by utilization of short-end injection capillary electrophoresis mode

Authors

ŘEMÍNEK, Roman, Jochen PAUWELS, Jos HOOGMARTENS, Ann VAN SCHEPDAEL and Zdeněk GLATZ

Edition

první. Brno, Czech Republic, Final Program & Book of Abstracts, 25th International Symposium on Microscale BioSeparations MSB 2010, p. 154-154, 1 pp. 2010

Publisher

Institute of Analytical Chemistry AS CR, v.v.i.

Other information

Language

English

Type of outcome

Stať ve sborníku

Field of Study

10600 1.6 Biological sciences

Country of publisher

Czech Republic

Confidentiality degree

není předmětem státního či obchodního tajemství

Organization unit

Faculty of Science

ISBN

978-80-254-6631-5

Keywords (in Czech)

kapilární elektroforéza, stabilita léčiv, HLM

Keywords in English

capillary electrophoresis, drug stability, HLM

Abstract

ORIG CZ

V originále

During a new drug development, the pharmaceutical companies endeavour to predict action of enzymes on the given new drug candidate within human body. This knowledge enables to omit the substances with inappropriate qualities and thus simplify implementation of the following tests. The current methods of drug stability assessment based on incubations with whole hepatocytes or even liver slices are laborious and time-consuming nevertheless. In this regard, the human liver microsomes (HLM) provide possibility of unfavourable state circumvent, because they offer advantage of fast analysis combined with preservation of realistic simulation of conditions inside the liver. The goal of this study was to introduce a new method based on the capillary electrophoresis (CE) allowing assessment of new drug candidate stability against HLM. Since, HLM contain high concentrations of membrane-bond proteins, the short-end injection CE mode was used to reduce the time spend by sample inside the capillary. A replaceable polymeric gel as a background electrolyte was used either to avoid the adsorption of sample components onto inner capillary wall in order to ensure high reproducibility of the method. Considering the large variety of possible new drug candidates, the method based on NADP production monitoring was hired rather than usually used measurement of substrate consumption or product creation, respectively. In this manner, the method allows analysis of every compound with does not co-migrate with NADP. As result the generic method enabling fast determination of new drug candidate stability was established. The method's validation showed an RSD of 1.77 % for migration time (n = 6), an RSD of 2.04 % for relative peak areas (n = 6) for NADP. Finally, method's potentiality was proved by carrying out of fast screen of 12 chosen probe drugs.

In Czech

Byla vypracována univerzální metoda pro rychlé stanovení stability léčiv vůči lidským jaterním mikrosomům pomocí kapilární elektroforézy.

Links

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

LC06023, research and development project

Name: Integrované bioanalytické technologie pro mikroanalýzy a diagnostiku s využitím LIF a hmotnostní spektrometrie

Investor: Ministry of Education, Youth and Sports of the CR

MSM0021622413, plan (intention)

Name: Proteiny v metabolismu a při interakci organismů s prostředím

Investor: Ministry of Education, Youth and Sports of the CR, Proteins in metabolism and interaction of organisms with the environment

Citovat

ŘEMÍNEK, Roman, Jochen PAUWELS, Jos HOOGMARTENS, Ann VAN SCHEPDAEL and Zdeněk GLATZ. Determination of drug stability against human liver microsomes by utilization of short-end injection capillary electrophoresis mode. In Final Program & Book of Abstracts, 25th International Symposium on Microscale BioSeparations MSB 2010. první. Brno, Czech Republic: Institute of Analytical Chemistry AS CR, v.v.i., 2010, p. 154-154. ISBN 978-80-254-6631-5.

@inproceedings{898940,
   author = {Řemínek, Roman and Pauwels, Jochen and Hoogmartens, Jos and Van Schepdael, Ann and Glatz, Zdeněk},
   address = {Brno, Czech Republic},
   booktitle = {Final Program & Book of Abstracts, 25th International Symposium on Microscale BioSeparations MSB 2010},
   edition = {první},
   keywords = {capillary electrophoresis, drug stability, HLM},
   language = {eng},
   location = {Brno, Czech Republic},
   isbn = {978-80-254-6631-5},
   pages = {154-154},
   publisher = {Institute of Analytical Chemistry AS CR, v.v.i.},
   title = {Determination of drug stability against human liver microsomes by utilization of short-end injection capillary electrophoresis mode},
   year = {2010}
}

TY  - JOUR
ID  - 898940
AU  - Řemínek, Roman - Pauwels, Jochen - Hoogmartens, Jos - Van Schepdael, Ann - Glatz, Zdeněk
PY  - 2010
TI  - Determination of drug stability against human liver microsomes by utilization of short-end injection capillary electrophoresis mode
PB  - Institute of Analytical Chemistry AS CR, v.v.i.
CY  - Brno, Czech Republic
SN  - 9788025466315
KW  - capillary electrophoresis, drug stability, HLM
N2  - During a new drug development, the pharmaceutical companies endeavour to predict action of enzymes on the given new drug candidate within human body. This knowledge enables to omit the substances with inappropriate qualities and thus simplify implementation of the following tests. The current methods of drug stability assessment based on incubations with whole hepatocytes or even liver slices are laborious and time-consuming nevertheless. In this regard, the human liver microsomes (HLM) provide possibility of unfavourable state circumvent, because they offer advantage of fast analysis combined with preservation of realistic simulation of conditions inside the liver. The goal of this study was to introduce a new method based on the capillary electrophoresis (CE) allowing assessment of new drug candidate stability against HLM. Since, HLM contain high concentrations of membrane-bond proteins, the short-end injection CE mode was used to reduce the time spend by sample inside the capillary. A replaceable polymeric gel as a background electrolyte was used either to avoid the adsorption of sample components onto inner capillary wall in order to ensure high reproducibility of the method. Considering the large variety of possible new drug candidates, the method based on NADP production monitoring was hired rather than usually used measurement of substrate consumption or product creation, respectively. In this manner, the method allows analysis of every compound with does not co-migrate with NADP. As result the generic method enabling fast determination of new drug candidate stability was established. The method's validation showed an RSD of 1.77 % for migration time (n = 6), an RSD of 2.04 % for relative peak areas (n = 6) for NADP. Finally, method's potentiality was proved by carrying out of fast screen of 12 chosen probe drugs.
ER  -

ŘEMÍNEK, Roman, Jochen PAUWELS, Jos HOOGMARTENS, Ann VAN SCHEPDAEL and Zdeněk GLATZ. Determination of drug stability against human liver microsomes by utilization of short-end injection capillary electrophoresis mode. In \textit{Final Program \&{} Book of Abstracts, 25th International Symposium on Microscale BioSeparations MSB 2010}. první. Brno, Czech Republic: Institute of Analytical Chemistry AS CR, v.v.i., 2010, p.~154-154. ISBN~978-80-254-6631-5.

Detailed Information on Publication Record