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

作者：Wen, Jian; Bao, Susu; Cai, Yaoyao; Zhang, Bowen; Wang, Rongrong; Wang, Chenchen; Hu, Guoxin^*

来源：Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences, 2017, 1068: 84-89.

DOI：10.1016/j.jchromb.2017.10.007

• Brigatinib
• UPLC-MS/MS
• Rat
• Pharmacoldnetics
• NSCLCI

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 (2.1 mm x 50 mm, 1.7 mu m). 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 (0.56 min) and imatinib (IS, 1.41 min). MS/MS detection was performed in positive mode. And the MRM transitions were m/z 584.09 -> 484.08 and m/z 494.3 -> 394.2 for brigatinib and IS, respectively. This method was assessed to be stable, specificity, and no matrix effect in three concentrations (0.004, 0.4, 4 mu g/mL). The intra-day and inter-day precisions were less than 11.09% and 6.43%. And infra-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 0.002-5 mu g/mL. The presented method was effectively implemented to determine the concentration of brigatinib in rat plasma.

• 出版日期2017-11-15
• 单位温州医科大学