Monique Zangarini1, Philip Berry1, Julieann Sludden1, Florence I Raynaud2, Udai Banerji2, Paul Jones3, David Edwards3, Gareth J Veal1. 1. Newcastle Cancer Centre Pharmacology Group, Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, NE2 4HH2, UK. 2. Cancer Research UK Cancer Therapeutics Unit, Division of Cancer Therapeutics, The Institute of Cancer Research, London, SM2 5NG3, UK. 3. Cancer Research UK Centre for Drug Development, London, EC1V 4AD, UK.
Abstract
AIM: SRA737 is an orally active small-molecule inhibitor of checkpoint kinase 1 being investigated in an oncology setting. A HPLC-MS/MS method for quantifying plasma concentrations of SRA737 was validated. METHODS & RESULTS: Sample preparation involved protein precipitation with acetonitrile following addition of 13C15N-deuterated SRA737 as internal standard. A rapid and selective method was fully validated across a range of 5-20,000 ng/ml, exhibiting good sensitivity, overall precision (expressed as coefficient of variation) ≤8.0% and accuracy 96-102%. Consistently high recovery was observed, with no matrix effect and a lower limit of quantitation of 5 ng/ml. CONCLUSION: A novel method for analyzing SRA737 in human plasma has been validated and is now being utilized for quantification of SRA737 in a Phase I trial.
AIM: SRA737 is an orally active small-molecule inhibitor of checkpoint kinase 1 being investigated in an oncology setting. A HPLC-MS/MS method for quantifying plasma concentrations of SRA737 was validated. METHODS & RESULTS: Sample preparation involved protein precipitation with acetonitrile following addition of 13C15N-deuterated SRA737 as internal standard. A rapid and selective method was fully validated across a range of 5-20,000 ng/ml, exhibiting good sensitivity, overall precision (expressed as coefficient of variation) ≤8.0% and accuracy 96-102%. Consistently high recovery was observed, with no matrix effect and a lower limit of quantitation of 5 ng/ml. CONCLUSION: A novel method for analyzing SRA737 in human plasma has been validated and is now being utilized for quantification of SRA737 in a Phase I trial.
Entities:
Keywords:
CCT245737; CHK1; LC–MS/MS; SRA737; cancer; pharmacokinetics; validation study