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
基于光滑粒子流体动力学方法(Smoothed Particle Hydrodynamics,SPH),开展了SPH新算法在蒸发燃烧领域的研究。建立了适用于SPH方法的蒸发数值模型,推导了基于傅立叶热传导公式和菲克扩散定律的SPH离散方程;借鉴VOF方法(Volume of Fluid...基于光滑粒子流体动力学方法(Smoothed Particle Hydrodynamics,SPH),开展了SPH新算法在蒸发燃烧领域的研究。建立了适用于SPH方法的蒸发数值模型,推导了基于傅立叶热传导公式和菲克扩散定律的SPH离散方程;借鉴VOF方法(Volume of Fluid)的思想,提出了SPH粒子的液相质量分数的概念,以有效表征蒸发过程中的相变问题。采用SPH方法对高温环境中单个液滴的蒸发过程进行数值模拟,结果符合D2定律,与理论模型相一致;在强迫对流环境中,液滴的蒸发过程受到对流作用及表面张力的影响,蒸发速率加快;进一步对双液滴在静止、对流环境中的蒸发过程进行数值模拟研究。结果表明,液滴的间距、滴径对多个液滴的蒸发过程影响至关重要,液滴间距至少在两倍的液滴直径以上,相互之间的影响才可以近似忽略。通过本文研究,拓宽了SPH方法在蒸发相变领域的应用范围,研究结果也能够为进一步的燃烧问题研究奠定基础。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.
文摘基于光滑粒子流体动力学方法(Smoothed Particle Hydrodynamics,SPH),开展了SPH新算法在蒸发燃烧领域的研究。建立了适用于SPH方法的蒸发数值模型,推导了基于傅立叶热传导公式和菲克扩散定律的SPH离散方程;借鉴VOF方法(Volume of Fluid)的思想,提出了SPH粒子的液相质量分数的概念,以有效表征蒸发过程中的相变问题。采用SPH方法对高温环境中单个液滴的蒸发过程进行数值模拟,结果符合D2定律,与理论模型相一致;在强迫对流环境中,液滴的蒸发过程受到对流作用及表面张力的影响,蒸发速率加快;进一步对双液滴在静止、对流环境中的蒸发过程进行数值模拟研究。结果表明,液滴的间距、滴径对多个液滴的蒸发过程影响至关重要,液滴间距至少在两倍的液滴直径以上,相互之间的影响才可以近似忽略。通过本文研究,拓宽了SPH方法在蒸发相变领域的应用范围,研究结果也能够为进一步的燃烧问题研究奠定基础。
