Ultra performance liquid chromatography tandem mass spectrometric method development and validation for determination of neratinib in human plasma

Abstract

This study was designed to develop and validate a UPLC-MS/MS method for quantification of neratinib in human plasmsa. Neratinib is an irreversible tyrosine kinase inhibitor against the pan-ErbB (ErbB-1, -2, -4) receptor. UPLC-MS/MS is an excellent analytical methodology for rapid biomedical analysis, decreasing the time for analysis and maintaining good efficiency. Crizotinib was used as internal standard (IS). Samples where extracted by plasma protein precipitation (PPT) procedure with acetonitrile and methanol and analysis was performed on a C 18 Acquity UPLC BEH™ column. The ion transitions where recorded in positive ion multiple reaction monitoring mode m/z 557.51→ 112.17 for neratinib and m/z 450.0 → 260.0 for IS. The mobile phase used was methanol:water: formic acid (70:30:0.1%, v/v/v) with a flow rate of 0.3 mL min -1. The linearity of the assay was found to be 4-500 ng mL -1 for neratinib in human plasma with lower limit of quatification of 4 ng mL -1. The intra- and inter-assay precision relative standard deviations did not exceed 10.99 and mean extraction recovery was found to be 69.12 ± 3.58.