An UPLC–MS/MS method for the quantitation of alectinib in rat plasma

摘要: Currently, crizotinib is the first generation drug, which has been used in treatment of ALK-rearranged non-small cell lung cancer (NSCLC). However, more and patients are found crizotinib-resistance. In last year, alectinib approved for with this study, we aim to develop validate a simple, rapid sensitive tandem mass spectrometry (UHPLC-MS/MS) method determination rat plasma. Diazepam was chosen as an internal standard (IS). Protein precipitation by acetonitrile utilized prepare plasma samples. Chromatographic separation achieved on RRHD Eclipse Plus C18 (2.1×50mm, 1.8μ) column gradient mobile phase consisting water (containing 0.1% formic acid). The analytes were detected electrospray ionization (ESI) source positive mode. A dynamic multiple reaction monitoring (MRM) developed detect specific precursor product ions. target fragment ions m/z 483.2→396.1 285.0→192.9 diazepam Linear calibration plots range 1-500ng/ml (R2=0.997) Mean recoveries ranged from 84.2% 92.2%. intra- inter-day precision below 9.3% accuracy -1.4% 12.1%. No obvious matrix effect found. This shows good performance: accuracy, stability. It fully validated successfully applied pharmacokinetic study alectinib.