Xun Bao, Jianmei Wu, Nader Sanai, Jing Li. A liquid chromatography with tandem mass spectrometry method for quantitating total and unbound ceritinib in patient plasma and brain tumor[J]. Journal of Pharmaceutical Analysis, 2018, 8(1): 20-26.
Citation:
Xun Bao, Jianmei Wu, Nader Sanai, Jing Li. A liquid chromatography with tandem mass spectrometry method for quantitating total and unbound ceritinib in patient plasma and brain tumor[J]. Journal of Pharmaceutical Analysis, 2018, 8(1): 20-26.
Xun Bao, Jianmei Wu, Nader Sanai, Jing Li. A liquid chromatography with tandem mass spectrometry method for quantitating total and unbound ceritinib in patient plasma and brain tumor[J]. Journal of Pharmaceutical Analysis, 2018, 8(1): 20-26.
Citation:
Xun Bao, Jianmei Wu, Nader Sanai, Jing Li. A liquid chromatography with tandem mass spectrometry method for quantitating total and unbound ceritinib in patient plasma and brain tumor[J]. Journal of Pharmaceutical Analysis, 2018, 8(1): 20-26.
Karmanos Cancer Institute,Wayne State University,Detroit,MI 48201,USA
Barrow Neurological Institute,St.Joseph's Hospital & Medical Center,Phoenix,AZ 85013,USA
Funds:
This study was supported by the United States Public Health Service Cancer Center Support Grant P30 CA022453. We thank Novartis for providing the study drug and isotope-labeled internal standard and providing financial support for the clinical study. We particularly thank the patients enrolled in th
A rapid,sensitive,and robust reversed-phase liquid chromatography with tandem mass spectrometrymethod was developed and validated for the determination of total and unbound ceritinib,a secondgenerationALK inhibitor,in patient plasma and brain tumor tissue samples.Sample preparation involvedsimple protein precipitation with acetonitrile.Chromatographic separation was achieved on a Waters ACQUITYUPLC BEH C18 column using a 4-min gradient elution consisting of mobile phase A(0.1% formic acidinwater)andmobile phase B(0.1% formic acid in acetonitrile),at a flow rate of 0.4 mL/min.Ceritinib and theinternal standard([13C6]ceritinib)were monitored using multiple reaction monitoring mode under positiveelectrospray ionization.The lower limit of quantitation(LLOQ)was 1 nM of ceritinib in plasma.The calibrationcurve was linear over ceritinib concentration range of 1–2000 nM in plasma.The intra-and interdayprecision 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 unbounddrug brain concentration to unbound drug plasma concentration ratio,in patients with brain tumors.