Open AccessDevelopment and validation of a LC–MS/MS method for the quantification of the checkpoint kinase 1 inhibitor SRA737 in human plasma
Author(s) -
Monique Zangarini,
Philip Berry,
Julieann Sludden,
Florence I. Raynaud,
Udai Banerji,
Paul S. Jones,
David I. Edwards,
Gareth J. Veal
Publication year - 2017
Publication title -
bioanalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.566
H-Index - 58
eISSN - 1757-6199
pISSN - 1757-6180
DOI - 10.4155/bio-2017-0043
Subject(s) - chromatography , protein precipitation , coefficient of variation , human plasma , chemistry
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 13 C 15 N-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.