Preclinical pharmacokinetics and tissue distribution of a novel multikinase inhibitor BZG by validated UPLC-MS/MS assay

Abstract

A simple and sensitive UPLC-MS/MS assay was developed and validated for rapid determination of BZG in rat plasma and tissues. All biological samples were prepared by protein precipitation method using Imatinib as an internal standard (IS). The analyte and IS were separated on a C18 reverse phase analytical column with 4.5 min of analytical run, at flow rate of 0.3 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer equipped with electrospray ionization (ESI) by multiple reactions monitoring (MRM) of the transitions at m/z 451.0→254.0 for BZG and m/z 494.3→394.1 for IS, respectively. The linearity of this method was found to be within the concentration range of 0.5-2500 ng/mL with a lower limit of quantification of 0.5 ng/mL. All validation parameter results were within the acceptable range described in guideline for bioanalytical method validation. The method was successfully applied to a pharmacokinetic and tissue distribution study of BZG in rats. With the preliminary knowledge of in vivo pharmacokinetics and disposition properties, this study will be beneficial for further development of BZG.

Keywords: BZG; Multikinase inhibitor; Novel sorafenib analogues; Pharmacokinetics; Tissue distribution; UPLC–MS/MS.