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.
Keywords: CCT245737; CHK1; LC–MS/MS; SRA737; cancer; pharmacokinetics; validation study.