Determination of selumetinib, N-desmethyl selumetinib and selumetinib amide in human biological samples by LC–MS/MS. (September 2016)

• Record Type: Journal Article
• Authors: Severin, Paul; Bailey, Christopher; Chen, Meng; Fisher, Ashley; Holmes, Victoria
• Is Part Of: Bioanalysis. Volume 8:Number 18(2016)
• Page Start: 1919
• Page End: 1936
• Publication Date: 2016-09
• Subjects: blood dialysate -- clinical -- LC–MS/MS -- oncology -- plasma -- plasma ultrafiltrate -- selumetinib -- urine -- validation; Drugs -- Analysis -- Periodicals; 615.19005
• DOI: 10.4155/bio-2016-0082
• Languages: English
• ISSNs: 1757-6180

Abstract

Aim: Selumetinib is an inhibitor of MEK1/2 in Phase III development that has activity in multiple tumor types. Validated bioanalytical methods were required to quantitate selumetinib and its N-desmethyl and amide metabolites in a variety of human biological matrices.Methodology & results: LC–MS/MS assays were developed and validated that demonstrated acceptable precision, accuracy and selectivity for selumetinib and the two metabolites in human plasma, urine, blood dialysate and plasma ultrafiltrate. Incurred sample re-analysis was acceptable and issues observed in plasma with the amide metabolite, due to potential instability, were addressed.Conclusion: Robust and sensitive LC–MS/MS assays for the quantification of selumetinib and two of its metabolites were validated in human biological matrices and are being used to support the clinical development program.