Quantitative LC-MS/MS method development and validation for the estimation of neratinib: application to bioavailability study in healthy rabbits

Abstract

A sensitive, simple and liquid chromatography – tandem mass spectrometry (LC- MS/MS) method was developed and  validated  for  the  fast  quantification of  Neratinib  (NRTB)  in  human  plasma.  The  developed method  was successfully applied to bioavailability study in healthy rabbits. The analyte and Crizotinib (CZNB) internal standard (IS) were separated from 200 mL of plasma sample by opting the protein precipitation as an extraction method with methanol.  Chromatographic  resolution  was  resolved  with  phenominex  C18(50mm×4.6  mm,  4  mm)  analytical nonpolar column and a mobile phase mixture of 10mM ammonium acetate, acetonitrile and methanol in the ratio of 20:30:50. Mobile phase flow from the column was fixed at 0.8 ml/min. The overall analysis time is promising compared to other reported procedures for Neratinib. From in vivo studies NRTB was shown Tmax of 6.05±0.027 and mean Cmax,  AUC0®t and AUC0®a  for test formulation is 295.83±39.066, 856.70 ± 153.16 and 1652.447 ± 205.06 respectively. The developed and validated research method was successfully applied in bioavailability studies in healthy rabbits.