A liquid chromatography with tandem mass spectrometry method for quantitating total and unbound ceritinib in patient plasma and brain tumor

作     者：Xun Bao Jianmei Wu Nader Sanai Jing Li 

作者机构：Karmanos Cancer Institute Wayne State University Barrow Neurological Institute St. Joseph's Hospital& Medical Center 

出 版 物：《Journal of Pharmaceutical Analysis》 (药物分析学报（英文版）)

年 卷 期：2018年第8卷第1期

页      面：20-26页

核心收录：

学科分类：10[医学] 

基　　金：supported by the United States Public Health Service Cancer Center Support Grant P30 CA022453 Novartis for providing the study drug and isotope-labeled internal standard and providing financial support for the clinical study 

主　　题：Ceritinib Reversed-phase liquid chromatography with tandem mass spectrometry (LC–MS/MS) Fraction unbound in plasma Fraction unbound in brain tissue Brain tumor penetration Unbound brain-to-plasma partition coefficient 

摘      要：A rapid, sensitive, and robust reversed-phase liquid chromatography with tandem mass spectrometry method was developed and validated for the determination of total and unbound ceritinib, a secondgeneration ALK inhibitor, in patient plasma and brain tumor tissue samples. Sample preparation involved simple protein precipitation with acetonitrile. Chromatographic separation was achieved on a Waters ACQUITY UPLC BEH C_(18) column using a 4-min gradient elution consisting of mobile phase A(0.1% formic acid in water) and mobile phase B(0.1% formic acid in acetonitrile), at a flow rate of 0.4 m L/min. Ceritinib and the internal standard([^(13)C_6]ceritinib) were monitored using multiple reaction monitoring mode under positive electrospray ionization. The lower limit of quantitation(LLOQ) was 1 n M of ceritinib in plasma. The calibration curve was linear over ceritinib concentration range of 1–2000 n M in plasma. The intra-and interday precision and accuracy were within the generally accepted criteria for bioanalytical method( o15%).The method was successfully applied to assess ceritinib brain tumor penetration, as assessed by the unbound drug brain concentration to unbound drug plasma concentration ratio, in patients with brain tumors.