Preferential solvation of pomalidomide(PMD)was explored in dimethyl sulfoxide(DMSO)-dimethylformamide(DMF),DMSO-tetrahydrofuran(THF),DMSO-methanol(Me OH),DMSO-isopropanol,DMSO-water,water-DMF,water-THF,water-Me OH,and...Preferential solvation of pomalidomide(PMD)was explored in dimethyl sulfoxide(DMSO)-dimethylformamide(DMF),DMSO-tetrahydrofuran(THF),DMSO-methanol(Me OH),DMSO-isopropanol,DMSO-water,water-DMF,water-THF,water-Me OH,and water–isopropanol binary mixed solvents at 298.15 K.Bosch-Rose model was utilized to determine the electronic transition energies(ET)and other preferential solvation parameters,describing solute-solute and solute-solvent interactions.We found thatλmaxsituation shifted with dielectric constant of the pure solvents meaningfully.According to the obtained results,ETenhanced andλmaxshifted to the lower wavelengths as the percentage of DMSO decreased in the binary mixtures,remarking the important role of DMSO for stabilizing the excited state(π*)of PMD chromophore via efficient intermolecular solute-solvent interactions.In addition,the aqueous binary systems showed an optimum point for the ETvalues as the percentage of water changed in the solutions.The local mole fraction of the solvents in the cybotactic region was also estimated to describe the specific and non-specific interactions in the systems.展开更多
Pomalidomide is an immunomodulatory agent (IMiD) that has been approved by the US Food and Drug Administration (FDA) for clinical treatment of patients with multiple myeloma.In this work,we developed a sensitive and v...Pomalidomide is an immunomodulatory agent (IMiD) that has been approved by the US Food and Drug Administration (FDA) for clinical treatment of patients with multiple myeloma.In this work,we developed a sensitive and validated LC-MS/MS method for high-throughput determination of pomalidomide over the range of 1.006-100.6 ng/mL(R^(2)=0.9991) in human plasma and pharmacokinetic studies.A liquid-liquid extraction method using ethyl acetate was applied to extract pomalidomide and afatinib (as an internal standard,IS) from human plasma.Chromatographic separation was performed on a Hedera ODS column (150 mm×2.1 mm,5μm) with security guard C18 column (4 mm×2.0 mm) at 40℃.Methanol and 10 mmol/L aqueous solution of ammonium acetate containing 0.1%formic acid were used as a gradient elution mobile phase,and the flow rate was 0.4 mL/min.A triple quadruple tandem mass spectrometer using multiplex reaction monitoring mode (MRM) with electrospray ionization (ESI) positive ionization was employed.The precursor to product ion transitions for the quantitative analysis of pomalidomide and the IS were m/z 274.2→163.1 and m/z 486.1→371.1,respectively.This established method has been validated according to regulatory guideline,and the results were all within the acceptance criteria.The validated LC-MS/MS method was successfully applied to analyze samples obtained from clinical pharmacokinetics study after oral administration of pomalidomide (4 mg) capsules in human.展开更多
文摘Preferential solvation of pomalidomide(PMD)was explored in dimethyl sulfoxide(DMSO)-dimethylformamide(DMF),DMSO-tetrahydrofuran(THF),DMSO-methanol(Me OH),DMSO-isopropanol,DMSO-water,water-DMF,water-THF,water-Me OH,and water–isopropanol binary mixed solvents at 298.15 K.Bosch-Rose model was utilized to determine the electronic transition energies(ET)and other preferential solvation parameters,describing solute-solute and solute-solvent interactions.We found thatλmaxsituation shifted with dielectric constant of the pure solvents meaningfully.According to the obtained results,ETenhanced andλmaxshifted to the lower wavelengths as the percentage of DMSO decreased in the binary mixtures,remarking the important role of DMSO for stabilizing the excited state(π*)of PMD chromophore via efficient intermolecular solute-solvent interactions.In addition,the aqueous binary systems showed an optimum point for the ETvalues as the percentage of water changed in the solutions.The local mole fraction of the solvents in the cybotactic region was also estimated to describe the specific and non-specific interactions in the systems.
基金financial support from National Natural Science Foundation of China (No.81603072)。
文摘Pomalidomide is an immunomodulatory agent (IMiD) that has been approved by the US Food and Drug Administration (FDA) for clinical treatment of patients with multiple myeloma.In this work,we developed a sensitive and validated LC-MS/MS method for high-throughput determination of pomalidomide over the range of 1.006-100.6 ng/mL(R^(2)=0.9991) in human plasma and pharmacokinetic studies.A liquid-liquid extraction method using ethyl acetate was applied to extract pomalidomide and afatinib (as an internal standard,IS) from human plasma.Chromatographic separation was performed on a Hedera ODS column (150 mm×2.1 mm,5μm) with security guard C18 column (4 mm×2.0 mm) at 40℃.Methanol and 10 mmol/L aqueous solution of ammonium acetate containing 0.1%formic acid were used as a gradient elution mobile phase,and the flow rate was 0.4 mL/min.A triple quadruple tandem mass spectrometer using multiplex reaction monitoring mode (MRM) with electrospray ionization (ESI) positive ionization was employed.The precursor to product ion transitions for the quantitative analysis of pomalidomide and the IS were m/z 274.2→163.1 and m/z 486.1→371.1,respectively.This established method has been validated according to regulatory guideline,and the results were all within the acceptance criteria.The validated LC-MS/MS method was successfully applied to analyze samples obtained from clinical pharmacokinetics study after oral administration of pomalidomide (4 mg) capsules in human.
