5 years ago

A reliable and stable method for determination of brigatinib in rat plasma by UPLC–MS/MS: Application to a pharmacokinetic study

Brigatinib is the second-generation anaplastic lymphoma kinase – inhibitor in non-small cell lung cancer and it can overcome the crizotinib-resistance. Chromatographic separation was carried out on an Acquity Ultra Performance Liquid Chromatography (UPLC) unit with a BEH C18 column (2.1mm×50mm, 1.7μm). The mobile phase was composed of acetonitrile and 0.1% formic acid in water. No endogenous interfering compounds was discovered at retention time of brigatinib (0.56min) and imatinib (IS, 1.41min). MS/MS detection was performed in positive mode. And the MRM transitions were m/z 584.09484.08 and m/z 494.3394.2 for brigatinib and IS, respectively. This method was assessed to be stable, specificity, and no matrix effect in three concentrations (0.004, 0.4, 4μg/mL). The intra-day and inter-day precisions were less than 11.09% and 6.43%. And intra-day and inter-day accuracies were ranged from −3.88% to 5.44%. The recovery of brigatinib was from 85.26% to 96.05%. Additionally, the method had a good linearity in the range of 0.002–5μg/mL. The presented method was effectively implemented to determine the concentration of brigatinib in rat plasma.

Publisher URL: www.sciencedirect.com/science

DOI: S1570023217313053

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