Development and validation of a LC–MS/MS method for the quantification of the checkpoint kinase 1 inhibitor SRA737 in human plasma. (July 2017)

• Record Type: Journal Article
• Authors: Zangarini, Monique; Berry, Philip; Sludden, Julieann; Raynaud, Florence I; Banerji, Udai; Jones, Paul; Edwards, David; Veal, Gareth J
• Is Part Of: Bioanalysis. Volume 9:Number 13(2017)
• Page Start: 1001
• Page End: 1010
• Publication Date: 2017-07
• Subjects: cancer -- CCT245737 -- CHK1 -- LC–MS/MS -- pharmacokinetics -- SRA737 -- validation study; Drugs -- Analysis -- Periodicals; 615.19005
• DOI: 10.4155/bio-2017-0043
• Languages: English
• ISSNs: 1757-6180

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 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.