ABSTRACT
@#Using high performance liquid chromatography and high resolution orbital trap mass spectrometry, a two-dimensional online desalting detection method was established to determine the structure of the impurities detected under the official testing conditions of lansoprazole enteric solution preparation, and a chromatographic method compatible with mass spectrometry was established to determine and presume the structure of the impurities that could not be separated by the the official testing method.The identification of impurity was to presume its structure according to the presence of impurity reference product, so as to investigate the difference of impurity spectrum of products from different manufacturers.The one-dimensional chromatographic conditions for the 2D online desalting method were the same as those in China Pharmacopoeia (2020) under relevant substances.Two-dimensional chromatography was performed on a Waters C18 T3 column (2.1 mm × 100 mm, 1.7 μm) with 0.1% formic acid in water-acetonitrile mobile phase and gradient elution.The chromatographic conditions for the compatible mass spectra were based on an Agilent Extend C18 (4.6 mm × 150 mm, 5 μm) column with mobile phase A: 25 mmol/L ammonium acetate and B: 25 mmol/L ammonium acetate-acetonitrile (1∶4) [pH adjusted to 6.5 with glacial acetic acid], with gradient elution. Nine impurities were detected by two-dimensional online desalting method, with 5 known impurities (A-E) and 4 unknown ones.14 impurities were detected by the compatible mass spectrometry method, with 9 unknown impurities (4 consistent with the results of two-dimensional online desalting method, and 5 newly detected).The structures and sources of the unknown impurities were deduced.The two detection methods of lansoprazole preparation by high-performance liquid chromatography-high resolution orbital trap mass spectrometry have guiding significance for quality control and process evaluation.
ABSTRACT
Objective To establish and analyze a mouse model of Staphylococcus aureus?induced arthritis ( Staphy?lococcus aureus septic arthritis, SA) , and provide an animal model for arthritis mechanism research and drug development. Methods Mice were immunosuppressed with cyclophosphamide, then intravenously inoculated with Staphylococcus au?reus. The gross characteristics of the joints were observed, the arthritis indexes were analyzed, and the pathological scores of the model mice were evaluated. Results From the first day after bacterial inoculation, the mouse joints were swollen. Pathological examination revealed lesions varying from mild and disarranged joint synovial hyperplasia to synovial thickening and intra?articular invasion, and increased neutrophil infiltration. Conclusions A mouse model of Staphylococcus aureus?induced arthritis is successfully established in this study. This model can be developed in a relatively short time, can not only simulate the clinical symptoms and signs and disease progression of human arthritis, but also to a certain extent reflects the etiology, infection and immunological mechanisms of human arthritis.
ABSTRACT
Objective The purpose of this study was to establish and evaluate a mouse model of sepsis for studying the mechanism of sepsis and development of anti-inflammatory drugs.Methods The sepsis in mice was induced by cecal ligation and puncture ( CLP) .The survival rates, microbial load, liver and kidney damages, cytokines and pathological changes were detected to evaluate the mouse models.Results The death of mice was closely related with the ligated sites. The mice with 50%cecal ligation displayed about 40% of 12-day survival rate, however, all the mice with 75% cecum ligation died within 4 days (P<0.01).Compared with the sham surgery group, the mice with 50% cecal ligation had a high microbial load in the blood and abdominal cavity.Leukopenia was also emerged (P<0.001).CLP mice demonstra-ted elevated levels of serum ALT, AST and BUN (P<0.01).The levels of IL1α, IL6, IL10, MIP1α, MIP1β, and TNFαwere increased a lot.The liver and lung showed obvious pathological injury at 48 h post CLP.Conclusions The established mouse model of CLP shows typical characteristics of sepsis and is an ideal tool for further study of anti-inflam-matory drugs.