D 2016

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

BITTOVÁ, Miroslava; Hana KOLÁŘOVÁ; Ondřej HYLSE; PrashantKumar KHIRSARIYA; Kamil PARUCH et al.

Základní údaje

Originální název

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

Vydání

Olomouc, Advances in chromatography and electrophoresis & Chiranal 2016, od s. 79-80, 2 s. 2016

Nakladatel

Palacký University, Olomouc

Další údaje

Jazyk

angličtina

Typ výsledku

Stať ve sborníku

Obor

10406 Analytical chemistry

Stát vydavatele

Česká republika

Utajení

není předmětem státního či obchodního tajemství

Forma vydání

tištěná verze "print"

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14310/16:00090180

Organizační jednotka

Přírodovědecká fakulta

ISBN

978-80-244-4961-6

Klíčová slova anglicky

LC-MS method; validation; chechpoint kinase 1 inhibitors
Změněno: 15. 6. 2016 09:42, Mgr. Miroslava Bittová, Ph.D.

Anotace

V originále

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.