Aim To determine five organic acids in Radix Isatidis . Method The extraction method and the column partition chromatographic conditions were studied. Then a capillary zone electrophoretic method was set up for t...Aim To determine five organic acids in Radix Isatidis . Method The extraction method and the column partition chromatographic conditions were studied. Then a capillary zone electrophoretic method was set up for the determination. Results The linear ranges of quinazolinone acid, n anthranilic acid, benzoic acid, salicylic acid, and syringic acid were 5 52-92 0 μg·mL -1 , 5 12-102 μg·mL -1 , 2 28-84 4 μg·mL-1 , 4 78-159 μg·mL -1 , and 1 74-87 0 μg·mL -1 respectively. Conclusion The established method is accurate and simple.展开更多
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
The thermodynamic partitioning behavior of solutes into immobilized artificial membrane(IAM) and n-octanol/water systems was investigated, including acidic,basic,and amphoteric substances.In an n-octanol/buffer system...The thermodynamic partitioning behavior of solutes into immobilized artificial membrane(IAM) and n-octanol/water systems was investigated, including acidic,basic,and amphoteric substances.In an n-octanol/buffer system,partitioning process was entropy-dominated for the most studied drugs,while partitioning of oxolinic and nalidixic acids into n-octanol phase was enthalpy-driven.In IAM chromatography,partitioning into membrane for the studied solutes was enthalpy-driven and an exothermal process.In conclusion,there is a significant difference of solutes′ partitioning mechanism into either IAM or an n-octanol phase,therefore,presenting the theoretical basis for differing lipophilicity measuring scale.展开更多
文摘Aim To determine five organic acids in Radix Isatidis . Method The extraction method and the column partition chromatographic conditions were studied. Then a capillary zone electrophoretic method was set up for the determination. Results The linear ranges of quinazolinone acid, n anthranilic acid, benzoic acid, salicylic acid, and syringic acid were 5 52-92 0 μg·mL -1 , 5 12-102 μg·mL -1 , 2 28-84 4 μg·mL-1 , 4 78-159 μg·mL -1 , and 1 74-87 0 μg·mL -1 respectively. Conclusion The established method is accurate and simple.
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The thermodynamic partitioning behavior of solutes into immobilized artificial membrane(IAM) and n-octanol/water systems was investigated, including acidic,basic,and amphoteric substances.In an n-octanol/buffer system,partitioning process was entropy-dominated for the most studied drugs,while partitioning of oxolinic and nalidixic acids into n-octanol phase was enthalpy-driven.In IAM chromatography,partitioning into membrane for the studied solutes was enthalpy-driven and an exothermal process.In conclusion,there is a significant difference of solutes′ partitioning mechanism into either IAM or an n-octanol phase,therefore,presenting the theoretical basis for differing lipophilicity measuring scale.
