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J Pharm Anal. 2018 Feb;8(1):20-26. doi: 10.1016/j.jpha.2017.07.007. Epub 2017 Jul 14.

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

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Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA.
Barrow Neurological Institute, St. Joseph's Hospital&Medical Center, Phoenix, AZ 85013, USA.


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 second-generation 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 C18 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 mL/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) was 1 nM of ceritinib in plasma. The calibration curve was linear over ceritinib concentration range of 1-2000 nM in plasma. The intra- and inter-day 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.


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

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