Development and validation of a highly sensitive LC-MS method for determination of checkpoint kinase 1 inhibitors in mouse plasma

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F16%3A00090180" target="_blank" >RIV/00216224:14310/16:00090180 - isvavai.cz</a>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Development and validation of a highly sensitive LC-MS method for determination of checkpoint kinase 1 inhibitors in mouse plasma

Popis výsledku v původním jazyce

Checkpoint kinase 1 (CHK1) belongs to the serine/threonine protein kinase family and its inhibition in combination with DNA replication stress results in apoptosis of tumour cells. Correspondingly, treatment with CHK1 inhibitors can enhance response to chemotherapy and decrease the amount of certain drugs used in cancer specific targeting therapy. In this work, we focused on development of a liquid chromatography method coupled to mass spectrometry (LC-MS) for determination of potent CHK1 inhibitors based on the pyrazolo[1,5-a]pyrimidine core. The main aim was determination of concentration of SCH 900776, its metabolite PK-03-22 and its fluorinated analogue OH209EN1 in mouse plasma. Prior to the LC-MS analysis, protein precipitation treatment of plasma sample was examined and optimized. Finally, the method was validated according to the FDA recommendations and currently it is being used for evaluation of pharmacokinetic profiles.

Název v anglickém jazyce

Development and validation of a highly sensitive LC-MS method for determination of checkpoint kinase 1 inhibitors in mouse plasma

Popis výsledku anglicky

Checkpoint kinase 1 (CHK1) belongs to the serine/threonine protein kinase family and its inhibition in combination with DNA replication stress results in apoptosis of tumour cells. Correspondingly, treatment with CHK1 inhibitors can enhance response to chemotherapy and decrease the amount of certain drugs used in cancer specific targeting therapy. In this work, we focused on development of a liquid chromatography method coupled to mass spectrometry (LC-MS) for determination of potent CHK1 inhibitors based on the pyrazolo[1,5-a]pyrimidine core. The main aim was determination of concentration of SCH 900776, its metabolite PK-03-22 and its fluorinated analogue OH209EN1 in mouse plasma. Prior to the LC-MS analysis, protein precipitation treatment of plasma sample was examined and optimized. Finally, the method was validated according to the FDA recommendations and currently it is being used for evaluation of pharmacokinetic profiles.

Druh

D - Stať ve sborníku

CEP obor

CB - Analytická chemie, separace

OECD FORD obor

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Projekt

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Návaznosti

S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2016

Kód důvěrnosti údajů

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

Název statě ve sborníku

Advances in chromatography and electrophoresis & Chiranal 2016

ISBN

9788024449616

ISSN

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e-ISSN

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Počet stran výsledku

2

Strana od-do

79-80

Název nakladatele

Palacký University, Olomouc

Místo vydání

Olomouc

Místo konání akce

Faculty of Science, Palacký University

Datum konání akce

6. 6. 2016

Typ akce podle státní příslušnosti

WRD - Celosvětová akce

Kód UT WoS článku

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