The modified shear lag model proposed recently was applied to calculate thermal residual stresses and subsequent stress distributions under tensile and compressive loadings. The expressions for the elastic moduli and ...The modified shear lag model proposed recently was applied to calculate thermal residual stresses and subsequent stress distributions under tensile and compressive loadings. The expressions for the elastic moduli and the yield strengths under tensile and compressive loadings were derived which take account of thermal residual stresses. The asymmetries in the elastic modulus and the yield strength were interpreted using the derived expressions and the obtained results of the stress calculations. The model predictions have exhibited good agreements with the experimental results and also with the other theoretical predictions展开更多
The South China Sea (SCS) is the largest marginal sea in West Pacific formed by a combined effect of the Eurasian plate, Pacific plate and India-Australian plate, and is thus considered to be a unique natural labora...The South China Sea (SCS) is the largest marginal sea in West Pacific formed by a combined effect of the Eurasian plate, Pacific plate and India-Australian plate, and is thus considered to be a unique natural laboratory to study oceanic dynamics and tectonic evolutions (Xie et al., 2006; Luan and Zhang, 2009). Besides, the SCS contains enormous petroleum resources for its favorable conditions of oil-gas generation, accumulation and preservation. It is therefore imperative to intensively study the marine in-situ stress and its controlling factors of the SCS.展开更多
Cetuximab (CTX) is a potent chimeric mouse/human monoclonal antibody (mAb) approved worldwide for treatment of metastatic colorectal cancer. Among the various biological and physical analyses per- formed for full ...Cetuximab (CTX) is a potent chimeric mouse/human monoclonal antibody (mAb) approved worldwide for treatment of metastatic colorectal cancer. Among the various biological and physical analyses per- formed for full study on this biopharmaceutic, the determination of the concentration preparations throughout manufacturing and subsequent handling in hospital is particularly relevant. In the present work, the study and validation of a method for quantifying intact CTX by reverse-phase high-perfor- mance liquid chromatography with diode array detection ((RP)HPLC/DAD) is presented. With that end, we checked the performance of a chromatographic method for quantifying CTX and conducted a study to validate the method as stability-indicating in accordance with the International Conference on Harmo- nization guidelines (ICH) for biotechnological drugs; therefore, we evaluated linearity, accuracy, preci- sion, detection and quantification limits, robustness and system suitability. The specificity of the method and the robustness of the mAb formulation against external stress factors were estimated by compre- hensive chromatographic analysis by subjecting CTX to several informative stress conditions. As de- monstrated, the method is rapid, accurate, and reproducible for CTX quantification. It was also suc- cessfully used to quantify CTX in a long-term stability study performed under hospital conditions.展开更多
YK- 1101, with its structure as S-((E)-4-((7S, 10S,Z)-4-ethylidene-7-isopropyl-2,5,8,12- tetraoxo -9-oxa- 16-thia-3,6,13,18-tetraazabicyclo[ 13.2.1 ]octadeca- 1 (17), 15( 18)-dien- 10-yl)but-3-en- 1 -y l) ...YK- 1101, with its structure as S-((E)-4-((7S, 10S,Z)-4-ethylidene-7-isopropyl-2,5,8,12- tetraoxo -9-oxa- 16-thia-3,6,13,18-tetraazabicyclo[ 13.2.1 ]octadeca- 1 (17), 15( 18)-dien- 10-yl)but-3-en- 1 -y l) ethanethioate, is synthesized as a potential histone deacetylase inhibitor. Its quality and stability under various stress conditions are not fully understood. In this study, a high performance liquid chromatographic (HPLC) method was established and validated for the analysis of YK-1101 bulk drug samples. The chromatographic separation was performed on a C18 column with acetonitrile and water as mobile phase in a gradient elution. Based on the established method, the stability studies of YK-1101 under various stress conditions were carried out. YK-1101 was shown to undergo degradation under basic and acidic stress conditions, while it was stable under oxidative, photolytic and thermal conditions. In addition~ a time of flight mass spectrometer (TOF/MS) was coupled to HPLC for the characterization of major degradation products produced under basic and acidic stress conditions. Their degradation pathways were also discussed.展开更多
The objective of current study was to develop a validated specific stability indicating reversed-phase liquid chromatographic method for the quantitative determination of desvenlafaxine in bulk sample and pharmaceutic...The objective of current study was to develop a validated specific stability indicating reversed-phase liquid chromatographic method for the quantitative determination of desvenlafaxine in bulk sample and pharmaceutical dosage form in the presence of degradation products. Forced degradation studies were performed on bulk sample of desvenlafaxine as per ICH prescribed stress conditions using acid, base, oxidative and photolytic degradation to show the stability indicating power of the method. Significant degradation was observed under acidic stress condition and the degradation product formed was identified by LC-MS and a degradation pathway for drug has been proposed. Successful separation of drug from degradation products formed under stress conditions was achieved on a SymmetryShield column C 18 (5 mm, 250 mm 4.6 mm, i.d.) using the mobile phase consisting of a mixture of 0.2% (v/v) triethylamine in ammonium acetate (0.05 M; pH 6.5) and methanol using isocratic gradient.展开更多
Pramipexole belongs to a class of nonergot dopamine agonist recently approved for the treatment of early and advanced Parkinson's disease.A validated specific stability indicating reversed-phase liquid chromatographi...Pramipexole belongs to a class of nonergot dopamine agonist recently approved for the treatment of early and advanced Parkinson's disease.A validated specific stability indicating reversed-phase liquid chromatographic method has been developed for the quantitative determination of pramipexole in bulk as well as in pharmaceutical dosage forms in the presence of degradation products.Forced degradation studies were performed by exposition of drug to hydrolytic(acidic and basic),oxidative and photolytic stress conditions,as defined under ICH guideline Q1A(R2).Significant degradation was observed under hydrolytic,oxidative and photolytic conditions and the degradation products formed were identified by LC-MS.展开更多
Immobilization leads not only to diminished joint movement but also low stress of articular cartilage. The present investigation was undertaken to observe the morphological changes which arose in articular cartilage w...Immobilization leads not only to diminished joint movement but also low stress of articular cartilage. The present investigation was undertaken to observe the morphological changes which arose in articular cartilage with low stress. The joint motion remained intact. Articular cartilage from the left knees of 66 rats whose left calcaneal tendons had been transected was examined under transmission electron microscope and light microscope. The degenerative changes were observed: decreased functional activity of chondrocytes progressively degenerated cartilage and lack of compensatory proliferation of chondrocytes at the early stage. We propose that the degeneration of articular cartilage induced by immobilization is the result of combination of low stress and lack of joint motion. The following degenerative mechanism begins with chondrocytes. Chondrocyte and matrix influence each other in a vicious cycle. Low stress may restrain the repair activities.展开更多
文摘The modified shear lag model proposed recently was applied to calculate thermal residual stresses and subsequent stress distributions under tensile and compressive loadings. The expressions for the elastic moduli and the yield strengths under tensile and compressive loadings were derived which take account of thermal residual stresses. The asymmetries in the elastic modulus and the yield strength were interpreted using the derived expressions and the obtained results of the stress calculations. The model predictions have exhibited good agreements with the experimental results and also with the other theoretical predictions
基金supported by the project of the China Geological Survey(Grant No.1212011220122)
文摘The South China Sea (SCS) is the largest marginal sea in West Pacific formed by a combined effect of the Eurasian plate, Pacific plate and India-Australian plate, and is thus considered to be a unique natural laboratory to study oceanic dynamics and tectonic evolutions (Xie et al., 2006; Luan and Zhang, 2009). Besides, the SCS contains enormous petroleum resources for its favorable conditions of oil-gas generation, accumulation and preservation. It is therefore imperative to intensively study the marine in-situ stress and its controlling factors of the SCS.
基金funded by Project FIS:PI10/00201 (Instituto Carlos III, Ministerio de Economía y Competitividad, Spain)partially supported by European Regional Development Funds (ERDF)
文摘Cetuximab (CTX) is a potent chimeric mouse/human monoclonal antibody (mAb) approved worldwide for treatment of metastatic colorectal cancer. Among the various biological and physical analyses per- formed for full study on this biopharmaceutic, the determination of the concentration preparations throughout manufacturing and subsequent handling in hospital is particularly relevant. In the present work, the study and validation of a method for quantifying intact CTX by reverse-phase high-perfor- mance liquid chromatography with diode array detection ((RP)HPLC/DAD) is presented. With that end, we checked the performance of a chromatographic method for quantifying CTX and conducted a study to validate the method as stability-indicating in accordance with the International Conference on Harmo- nization guidelines (ICH) for biotechnological drugs; therefore, we evaluated linearity, accuracy, preci- sion, detection and quantification limits, robustness and system suitability. The specificity of the method and the robustness of the mAb formulation against external stress factors were estimated by compre- hensive chromatographic analysis by subjecting CTX to several informative stress conditions. As de- monstrated, the method is rapid, accurate, and reproducible for CTX quantification. It was also suc- cessfully used to quantify CTX in a long-term stability study performed under hospital conditions.
基金supported by the postgraduate innovation foundation of Simcere (No. CX11S-002XS)
文摘YK- 1101, with its structure as S-((E)-4-((7S, 10S,Z)-4-ethylidene-7-isopropyl-2,5,8,12- tetraoxo -9-oxa- 16-thia-3,6,13,18-tetraazabicyclo[ 13.2.1 ]octadeca- 1 (17), 15( 18)-dien- 10-yl)but-3-en- 1 -y l) ethanethioate, is synthesized as a potential histone deacetylase inhibitor. Its quality and stability under various stress conditions are not fully understood. In this study, a high performance liquid chromatographic (HPLC) method was established and validated for the analysis of YK-1101 bulk drug samples. The chromatographic separation was performed on a C18 column with acetonitrile and water as mobile phase in a gradient elution. Based on the established method, the stability studies of YK-1101 under various stress conditions were carried out. YK-1101 was shown to undergo degradation under basic and acidic stress conditions, while it was stable under oxidative, photolytic and thermal conditions. In addition~ a time of flight mass spectrometer (TOF/MS) was coupled to HPLC for the characterization of major degradation products produced under basic and acidic stress conditions. Their degradation pathways were also discussed.
文摘The objective of current study was to develop a validated specific stability indicating reversed-phase liquid chromatographic method for the quantitative determination of desvenlafaxine in bulk sample and pharmaceutical dosage form in the presence of degradation products. Forced degradation studies were performed on bulk sample of desvenlafaxine as per ICH prescribed stress conditions using acid, base, oxidative and photolytic degradation to show the stability indicating power of the method. Significant degradation was observed under acidic stress condition and the degradation product formed was identified by LC-MS and a degradation pathway for drug has been proposed. Successful separation of drug from degradation products formed under stress conditions was achieved on a SymmetryShield column C 18 (5 mm, 250 mm 4.6 mm, i.d.) using the mobile phase consisting of a mixture of 0.2% (v/v) triethylamine in ammonium acetate (0.05 M; pH 6.5) and methanol using isocratic gradient.
文摘Pramipexole belongs to a class of nonergot dopamine agonist recently approved for the treatment of early and advanced Parkinson's disease.A validated specific stability indicating reversed-phase liquid chromatographic method has been developed for the quantitative determination of pramipexole in bulk as well as in pharmaceutical dosage forms in the presence of degradation products.Forced degradation studies were performed by exposition of drug to hydrolytic(acidic and basic),oxidative and photolytic stress conditions,as defined under ICH guideline Q1A(R2).Significant degradation was observed under hydrolytic,oxidative and photolytic conditions and the degradation products formed were identified by LC-MS.
文摘Immobilization leads not only to diminished joint movement but also low stress of articular cartilage. The present investigation was undertaken to observe the morphological changes which arose in articular cartilage with low stress. The joint motion remained intact. Articular cartilage from the left knees of 66 rats whose left calcaneal tendons had been transected was examined under transmission electron microscope and light microscope. The degenerative changes were observed: decreased functional activity of chondrocytes progressively degenerated cartilage and lack of compensatory proliferation of chondrocytes at the early stage. We propose that the degeneration of articular cartilage induced by immobilization is the result of combination of low stress and lack of joint motion. The following degenerative mechanism begins with chondrocytes. Chondrocyte and matrix influence each other in a vicious cycle. Low stress may restrain the repair activities.