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

Abstract

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.

• Authors: Xun Bao, Jianmei Wu, Nader Sanai, Jing Li
• Journal: Journal of pharmaceutical analysis (J Pharm Anal) Vol. 8 Issue 1 Pg. 20-26 (Feb 2018) ISSN: 2214-0883 [Electronic] China
• PMID: 29568664 (Publication Type: Journal Article)