Development and validation of a LC-MS/MS method for the quantification of the checkpoint kinase 1 inhibitor SRA737 in human plasma.
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Date
2017-07-01Author
Zangarini, M
Berry, P
Sludden, J
Raynaud, FI
Banerji, U
Jones, P
Edwards, D
Veal, GJ
Type
Journal Article
Metadata
Show full item recordAbstract
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.
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Subject
Humans
Protein Kinase Inhibitors
Blood Chemical Analysis
Chromatography, High Pressure Liquid
Linear Models
Tandem Mass Spectrometry
Limit of Detection
Heterocyclic Compounds, 4 or More Rings
Checkpoint Kinase 1
Research team
Clinical Pharmacology & Trials (including Drug Metabolism & Pharmacokinetics Group)
Clinical Pharmacology – Adaptive Therapy
Medicine Drug Development Unit (de Bono)
Language
eng
Date accepted
2016-04-02
License start date
2017-07-10
Citation
Bioanalysis, 2017, 9 (13), pp. 1001 - 1010
Publisher
FUTURE SCI LTD