Forced degradation study of argatroban under conditions of hydrolysis(neutral, acidic and alkaline), oxidation,photolysis and thermal stress, as suggested in the ICH Q1 A(R2), was accomplished. The drug showed signifi...Forced degradation study of argatroban under conditions of hydrolysis(neutral, acidic and alkaline), oxidation,photolysis and thermal stress, as suggested in the ICH Q1 A(R2), was accomplished. The drug showed significant degradation under hydrolysis(acidic, alkaline) and oxidation(peroxide stress) conditions. The drug remained stable under thermal and photolytic stress conditions. In total, seven novel degradation products(DP-1 to DP-7) were found under diverse conditions, which were not reported earlier. The chemical structures of these degradation products were characterized by ~1H NMR,^(13)C NMR, 2 D NMR, Q-TOF-MSnand IR spectral analysis and the proposed degradation products structures were further confirmed by the individual synthesis.展开更多
In order to identify the potential nephrotoxic compounds in traditional Chinese medicine Lithospermum erythrorhizon,it was separated into serial fractions according to their polarities.An in vitro method was utilized ...In order to identify the potential nephrotoxic compounds in traditional Chinese medicine Lithospermum erythrorhizon,it was separated into serial fractions according to their polarities.An in vitro method was utilized to determine the nephrotoxicity of these fractions with the help of fluorescence image analysis.As a result,the primary fraction A05 and its secondary fractions C06 ＂C09 and C12 ＂C14 were found to have significant toxicity to LLC-PK1 cell line,as determined by the survive rate less than 20% after they were treated with these fractions.These potential nephrotoxic fractions were further analyzed by multistage and high resolution mass spectrometry.The main compounds in these fractions were tentatively identified to be acetylshikonin,isobutyrylshikonin,β,β＇-dimethyla-cryloylshikonin,and isovalerylshikonin,which may bring nephrotoxicity.展开更多
文摘Forced degradation study of argatroban under conditions of hydrolysis(neutral, acidic and alkaline), oxidation,photolysis and thermal stress, as suggested in the ICH Q1 A(R2), was accomplished. The drug showed significant degradation under hydrolysis(acidic, alkaline) and oxidation(peroxide stress) conditions. The drug remained stable under thermal and photolytic stress conditions. In total, seven novel degradation products(DP-1 to DP-7) were found under diverse conditions, which were not reported earlier. The chemical structures of these degradation products were characterized by ~1H NMR,^(13)C NMR, 2 D NMR, Q-TOF-MSnand IR spectral analysis and the proposed degradation products structures were further confirmed by the individual synthesis.
基金Supported by the National Key Scientific and Technological Project of China(No.2009ZX09502-012)the Research Fund for the Doctoral Program of Higher Education of China(No.20090101110126)the Zhejiang Province Science and Technology Plan Project,China(No.2008C23065)
文摘In order to identify the potential nephrotoxic compounds in traditional Chinese medicine Lithospermum erythrorhizon,it was separated into serial fractions according to their polarities.An in vitro method was utilized to determine the nephrotoxicity of these fractions with the help of fluorescence image analysis.As a result,the primary fraction A05 and its secondary fractions C06 ＂C09 and C12 ＂C14 were found to have significant toxicity to LLC-PK1 cell line,as determined by the survive rate less than 20% after they were treated with these fractions.These potential nephrotoxic fractions were further analyzed by multistage and high resolution mass spectrometry.The main compounds in these fractions were tentatively identified to be acetylshikonin,isobutyrylshikonin,β,β＇-dimethyla-cryloylshikonin,and isovalerylshikonin,which may bring nephrotoxicity.
