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
The linearity, stability, accuracy and inter-day precisions of the assay method were evaluated in methanolic aerial-part extracts of Paepalanthus giganteus and Syngontnhus nitens from the Eriocaulaceae family. Their s...The linearity, stability, accuracy and inter-day precisions of the assay method were evaluated in methanolic aerial-part extracts of Paepalanthus giganteus and Syngontnhus nitens from the Eriocaulaceae family. Their small capitulae hinder morphological analysis, and thus complicate taxonomic studies of these species, which present anti-ulcer, antimutagenic and antioxidant activities. Taxonomic studies of these plants revealed that the Paepalanthus genus presents flavonols and naphthopyranones while the Syngontnhus genus has flavone and xanthone as majority compounds. The prepared samples were analyzed quantitatively by High Performance Liquid Chromatography with PDA detection for the presence of quercetin, luteolin, 3,6-dimethoxy-1,5,7-tri-hydroxyxanthone and paepalantine. The substances were recovered from these samples at rates from 98.01 to 99.99%. The coefficient of variation in the quantitative analysis of the sample com- pounds was under 5%. The linearity of the method was determined by linear regression. The analysis of the samples spiked with known amounts of analyte demonstrated that the response was proportional to the concentrations of the sam- ples with re-spective determination coefficients of r2 = 0.9999 (luteolin and 3,6-dimethoxy-1,5,7-tri-hydroxyxanthone) and r2 = 0.9998 (quercetin and paepalantine) for the linear range of the analytical calibration curves of the samples. The detection limits were 0.07 μg?mL–1 for quercetin and luteolin, 0.06 μg?mL–1 for 3,6-dimethoxy-1,5,7-tri-hydroxyxanthone and 0.10 μg?mL–1 for paepalantine. The quantification limits were 0.23 μg?mL–1 for quercetin and luteolin, 0.20 μg?mL–1 for 3,6-dimethoxy-1,5,7-tri-hydroxyxanthone and 0.33 μg?mL–1 for paepalantine by LC. The method was considered sen- sitive for quantification of the quercetin, luteolin, 3,6-dimethoxy-1,5,7-tri-hydroxyxanthone and paepalantine in plant samples.展开更多
Mevinolin is one of the earlier statin drugs which is effective for the treatment of hypercholesterolemia, as an inhibitor of the HMG-CoA reductase. The transformations of mevinolin in acidic alcohol（ such as ethanol...Mevinolin is one of the earlier statin drugs which is effective for the treatment of hypercholesterolemia, as an inhibitor of the HMG-CoA reductase. The transformations of mevinolin in acidic alcohol（ such as ethanol, methanol and isopropanol） solutions caused by solvent effects were revealed in the present article. The solvates, that is, mevinolinic methyl ester, mevinolinic ethyl ester and mevinolinic isopropyl ester, were identified by LC/PDA and LC/MS. The kinetics parameters of the transformations caused by solvent effects, such as the observed rate constant of mevinolin （kobs）, the maximum concentration（ Cmax ）, and its corresponding maximum time（ t time for the acid form to reach the maximum concentration） of mevinolinic acid, are discussed. The influencing factors, such as the kind of solvents, the acidic concentration, the initial mevinolin concentration, and the water content as well as temperature were investigated. Two kinds of comparative reactions, hydrolysis and alcoholysis, of mevinolin in solution were studied. This detailed study on the kinetics of mevinolin transformations is valuable and meaningful for the purification, preparation, injection manufacturing, extraction, storage, etc. , of mevinolin or other similar compounds. This work provides useful information for the quality control of mevinolin and mevinolin-like drugs as well.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the Fundacao de Amparo a Pesquisa do Estado de Sao Paulo(FAPESP),for fundingthe Conselho Nacional de Desenvolvimento Científico e Tecnologico(CNPq),for grants to L.C.Santos.
文摘The linearity, stability, accuracy and inter-day precisions of the assay method were evaluated in methanolic aerial-part extracts of Paepalanthus giganteus and Syngontnhus nitens from the Eriocaulaceae family. Their small capitulae hinder morphological analysis, and thus complicate taxonomic studies of these species, which present anti-ulcer, antimutagenic and antioxidant activities. Taxonomic studies of these plants revealed that the Paepalanthus genus presents flavonols and naphthopyranones while the Syngontnhus genus has flavone and xanthone as majority compounds. The prepared samples were analyzed quantitatively by High Performance Liquid Chromatography with PDA detection for the presence of quercetin, luteolin, 3,6-dimethoxy-1,5,7-tri-hydroxyxanthone and paepalantine. The substances were recovered from these samples at rates from 98.01 to 99.99%. The coefficient of variation in the quantitative analysis of the sample com- pounds was under 5%. The linearity of the method was determined by linear regression. The analysis of the samples spiked with known amounts of analyte demonstrated that the response was proportional to the concentrations of the sam- ples with re-spective determination coefficients of r2 = 0.9999 (luteolin and 3,6-dimethoxy-1,5,7-tri-hydroxyxanthone) and r2 = 0.9998 (quercetin and paepalantine) for the linear range of the analytical calibration curves of the samples. The detection limits were 0.07 μg?mL–1 for quercetin and luteolin, 0.06 μg?mL–1 for 3,6-dimethoxy-1,5,7-tri-hydroxyxanthone and 0.10 μg?mL–1 for paepalantine. The quantification limits were 0.23 μg?mL–1 for quercetin and luteolin, 0.20 μg?mL–1 for 3,6-dimethoxy-1,5,7-tri-hydroxyxanthone and 0.33 μg?mL–1 for paepalantine by LC. The method was considered sen- sitive for quantification of the quercetin, luteolin, 3,6-dimethoxy-1,5,7-tri-hydroxyxanthone and paepalantine in plant samples.
基金Supported by Shanghai Leading Discipline Project(No. Y0301) and the Funds of Shanghai Scientific and Technology Develop-ment(No. 03DZ19546)
文摘Mevinolin is one of the earlier statin drugs which is effective for the treatment of hypercholesterolemia, as an inhibitor of the HMG-CoA reductase. The transformations of mevinolin in acidic alcohol（ such as ethanol, methanol and isopropanol） solutions caused by solvent effects were revealed in the present article. The solvates, that is, mevinolinic methyl ester, mevinolinic ethyl ester and mevinolinic isopropyl ester, were identified by LC/PDA and LC/MS. The kinetics parameters of the transformations caused by solvent effects, such as the observed rate constant of mevinolin （kobs）, the maximum concentration（ Cmax ）, and its corresponding maximum time（ t time for the acid form to reach the maximum concentration） of mevinolinic acid, are discussed. The influencing factors, such as the kind of solvents, the acidic concentration, the initial mevinolin concentration, and the water content as well as temperature were investigated. Two kinds of comparative reactions, hydrolysis and alcoholysis, of mevinolin in solution were studied. This detailed study on the kinetics of mevinolin transformations is valuable and meaningful for the purification, preparation, injection manufacturing, extraction, storage, etc. , of mevinolin or other similar compounds. This work provides useful information for the quality control of mevinolin and mevinolin-like drugs as well.
