A highly sensitive LC-MS/MS method for quantification of a pan-erbB kinase inhibitor-PD168393 in plasma

摘要

Over expression of the epidermal growth factor receptor (EGFR) has been reported in a significant number of human tumors and is associated with poor prognosis. Inhibition of growth signal pathways mediated through EGFR tyrosine autophosphorylation is of therapeutic interest, and inhibitors of this process have been widely sought as potential anticancer drugs (1). PD168393 (4-[(3-Bromophenyl) amino]-6-acrylamidoquinazoline) is a pan-erbB kinase inhibitor (2). Recently, novel therapeutic approaches targeting the EGFR superfamily and their downstream pathways have been generated and PD168383 has attracted much attention as a cancer chemotherapeutic agent (2,3). The irreversible nature of this compound may offer potential advantage of target suppression and in vivo pharmacokinetics. To the best of our knowledge, there is no report using liquid chromatography tandem mass spectrometry (LC-MS/MS) for the quantitative analysis of PD168393. The objective of the investigation was to develop and validate a simple, selective and sensitive LC-MS/MS method for the quantification of PD168393 in biological samples to support pharmacokinetic studies in mice.