Development and validation of a LC-MS/MS method for the quantification of the checkpoint kinase 1 inhibitor SRA737 in human plasma.

Authors :: Zangarini M
Berry P
Sludden J
Raynaud FI
Banerji U
Jones P
Edwards D
Veal GJ
Source :: Bioanalysis [Bioanalysis] 2017 Jul; Vol. 9 (13), pp. 1001-1010. Date of Electronic Publication: 2017 Jul 10.
Publication Year :: 2017
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.<br />Methods & Results: Sample preparation involved protein precipitation with acetonitrile following addition of <superscript>13</superscript> C <superscript>15</superscript> 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.<br />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.

Subjects :: Heterocyclic Compounds, 4 or More Rings pharmacology
Humans
Limit of Detection
Linear Models
Protein Kinase Inhibitors pharmacology
Blood Chemical Analysis methods
Checkpoint Kinase 1 antagonists & inhibitors
Chromatography, High Pressure Liquid methods
Heterocyclic Compounds, 4 or More Rings blood
Protein Kinase Inhibitors blood
Tandem Mass Spectrometry methods

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