A validated UPLC-MS/MS assay of E7090, a novel selective inhibitor of fibroblast growth factor receptors, in human plasma and urine

E7090, a novel fibroblast growth factor receptors inhibitor, is currently under clinical development for the treatment of patients with solid tumors. Assays for the determination of E7090 concentrations in human plasma and urine have been developed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to evaluate pharmacokinetic profiles of E7090. E7090 and a deuterated labeled internal standard (IS) were extracted from 50 μL of plasma by protein precipitation. In quantification of E7090 in urine, 50 μL of urine samples fortified with 15 μL of ethanol (10:3, v/v) to minimize nonspecific binding of E7090 to urine containers were subjected to the assay without extraction. E7090 and the IS were separated by chromatography on a reverse phase column and were detected by selected reaction monitoring in the positive ion mode. The lower limit of quantification was set at 1 ng/mL and E7090 was quantifiable from 1 to 3000 ng/mL in plasma and urine. Accuracy and precision were measured during the reproducibility assessments and were within ± 7.0% and 9.1%, respectively, in plasma and within ± 7.0% and 5.8%, respectively, in urine, indicating sufficient reproducibility. The validated methods were successfully applied to the quantification of E7090 in human plasma and urine to support a Phase-1 clinical trial. •This is the first report of E7090 assay in human plasma and urine.•Non-specific binding in urine collection tubes was addressed by addition of ethanol.•The lower limit of quantification was 1 ng/mL in plasma and urine.•The developed method was successfully validated in accordance with bioanalytical guidelines.•The established method was applied to a Phase-1 clinical trial.