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

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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 C18column using a4-min gradient elution consisting of mobile phase A(0.1%formic acid inwater)andmobile phase B(0.1%formic acid in acetonitrile),at a flow rate of0.4mL/min.Ceritinib and the internal standard([13C6]ceritinib)were monitored using multiple reaction monitoring mode under positive electrospray ionization.The lower limit of quantitation(LLOQ)was1nM of ceritinib in plasma.The calibration curve was linear over ceritinib concentration range of1-2000nM in plasma.The intra-and interday precision and accuracy were within the generally accepted criteria for bioanalytical method(<15%).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.
出处 《药物分析学报:英文版》 CAS CSCD 2018年第1期20-26,共7页 Journal of Pharmaceutical Analysis
作者简介 Corresponding author.E-mail address:lijin@karmanos.org(J.Li).
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