Publication details
Development and validation of a highly sensitive LC-MS method for determination of checkpoint kinase 1 inhibitors in mouse plasma
| Authors | |
|---|---|
| Year of publication | 2016 |
| Type | Article in Proceedings |
| Conference | Advances in chromatography and electrophoresis & Chiranal 2016 |
| MU Faculty or unit | |
| Citation | |
| Field | Analytic chemistry |
| Keywords | LC-MS method; validation; chechpoint kinase 1 inhibitors |
| Description | 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. |