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.

Základní údaje

Originální název

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

Autoři

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

Vydání

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

Nakladatel

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

Další údaje

Jazyk

angličtina

Typ výsledku

Stať ve sborníku

Obor

10600 1.6 Biological sciences

Stát vydavatele

Česká republika

Utajení

není předmětem státního či obchodního tajemství

Organizační jednotka

Přírodovědecká fakulta

ISBN

978-80-254-6631-5

Klíčová slova česky

kapilární elektroforéza, stabilita léčiv, HLM

Klíčová slova anglicky

capillary electrophoresis, drug stability, HLM

Štítky

CE, drug stability, human liver microsomes, short end injection

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 13. 12. 2010 08:19, prof. RNDr. Zdeněk Glatz, CSc.

Anotace

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.

Česky

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

Návaznosti

GAP206/10/0057, projekt VaV

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

Investor: Grantová agentura ČR, Miniaturizovaný systém pro "on-line" studie metabolismu léčiv založený na kapilární elektroforéze

LC06023, projekt VaV

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

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Integrované bioanalytické technologie pro mikroanalýzy a diagnostiku s využitím LIF a hmotnostní spektrometrie

MSM0021622413, záměr

Název: Proteiny v metabolismu a při interakci organismů s prostředím

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Proteiny v metabolismu a při interakci organismů s prostředím

Citovat

ŘEMÍNEK, Roman, Jochen PAUWELS, Jos HOOGMARTENS, Ann VAN SCHEPDAEL a 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, s. 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 a 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, s.~154-154. ISBN~978-80-254-6631-5.

Podrobný výpis o publikaci