Simultaneous Quantification of Brigatinib and Brigatinib-Analog in Rat Plasma and Brain Homogenate by LC-MSMS: Application to Comparative Pharmacokinetic and Brain Distribution Studies

Abstract EN

Brigatinib and brigatinib-analog are potent and selective ALK inhibitors with the similar structure.

A simple and sensitive high-performance liquid chromatography with tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of brigatinib and brigatinib-analog in rat plasma and brain homogenate was developed and validated.

Chromatographic separation was carried out on an ODS column with acetonitrile and 0.1% formic acid in water as the mobile phase with gradient elution at a flow rate of 0.5 mL/min.

Detections were performed using a TSQ Quantum Ultra mass spectrometric detector with electrospray ionization (ESI) interface, which was operated in the positive ion mode.

A simple protein precipitation preparation process was used.

The lower limits of quantification (LLOQs) were 1.0 ng/mL and 0.5 ng/mL for analytes in rat plasma and brain homogenate, respectively.

The intrabatch and interbatch precision and accuracy of brigatinib and brigatinib-analog were well within the acceptable limits of variation.

The simple and sensitive LC-MS/MS method was successfully applied to the pharmacokinetic and brain distribution studies following a single oral administration of brigatinib and brigatinib-analog to rats.

The above studies would lay a good foundation for the further applications of brigatinib and brigatinib-analog.