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 inhibit...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.展开更多
In this paper, first of all we shall establish the Poincaré inequality in the Sobolev space (Ω) and Sobolev-Orlicz space (φ; Ω), where is an unbounded domain, and then generalize the result of [1] to the unbou...In this paper, first of all we shall establish the Poincaré inequality in the Sobolev space (Ω) and Sobolev-Orlicz space (φ; Ω), where is an unbounded domain, and then generalize the result of [1] to the unbounded domain. Thereto, we shall weaken the constrained condition of strong nonlinear variations. Signs in [1] and [3] are used.展开更多
基金supported by the United States Public Health Service Cancer Center Support Grant P30 CA022453Novartis for providing the study drug and isotope-labeled internal standard and providing financial support for the clinical study
文摘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.
文摘In this paper, first of all we shall establish the Poincaré inequality in the Sobolev space (Ω) and Sobolev-Orlicz space (φ; Ω), where is an unbounded domain, and then generalize the result of [1] to the unbounded domain. Thereto, we shall weaken the constrained condition of strong nonlinear variations. Signs in [1] and [3] are used.
