\ According to the analysis of the residual products by thermogravimetric analysis (TGA), the thermal decomposition process of cefazolin sodium (CEZ·Na) was thought to be similar to the degradation in solid sta...\ According to the analysis of the residual products by thermogravimetric analysis (TGA), the thermal decomposition process of cefazolin sodium (CEZ·Na) was thought to be similar to the degradation in solid state in its storage time. This laid a foundation for estimating the relative chemical stability of the drug by determination of its decomposition kinetics using TGA. Although the observed thermal decomposition kinetics of CEZ·Na was complex, a conversion level of 1% was chosen for evaluation of the stability of CEZ·Na crystalline since the mechanism here was more likely to be that of the actual product failure. The evaluation results suggested that the α form of CEZ·Na had the best stability and the amorphous one was the least stable one among α form, dehydrated α form and amorphous form.展开更多
A sensitive and specific high performance liquid chromatography method was established for measuring cefazolin sodium level in rabbit synovial fluid. Acetonitrile was used to precipitate proteins and antipyrine was us...A sensitive and specific high performance liquid chromatography method was established for measuring cefazolin sodium level in rabbit synovial fluid. Acetonitrile was used to precipitate proteins and antipyrine was used as internal standard. Samples were analyzed on a Dionex Ultimate U3000 HPLC system equipped with Phenomenex Luna C18 column （150 mmx4.60 mm, 5 Bm, 100 A）. The mobile phase consisted of acetonitrile and 0.1% formic acid in water. The flow rate was 1 mL/min. The detection wavelength was set at 272 nm. The column temperature was maintained at 25 ℃. The calibration curve was linear in the range of 1.0-100.0 μg/mL （r2 = 0.9999）. The limit of detection （LOD, S/N - 3） was 0.07 μg/mL. The limit of quantitation （LOD, S/N = 10） was 0.22 pg/mL. The recovery of cefazolin sodium （low, medium and high） was 124.6%, 117.8%, and 100.6% （RSD% - 1.9%, 4.0%, 1.1%, n = 5）, respectively. The intra-day and inter-day precision values were in the range of 0.5%-2.7%. The method was simple, sensitive and reliable. It can be used for the quantitative determination of cefazolin sodium in rabbit synovial fluid.展开更多
Cefazolin sodium can form both α- and β-form crystals. It also can form dehydrated crystalline and amorphous products through different production processes. Because different polymorphic medicines usually have diff...Cefazolin sodium can form both α- and β-form crystals. It also can form dehydrated crystalline and amorphous products through different production processes. Because different polymorphic medicines usually have different physical and chemical properties, it is critical to emphasize the crystallization control of polymorphic medicines. Near-infrared （NIR） analysis, which incorporates a combination of NIR spectroscopic techniques and multivariate chemometric methods, is considered a powerful tool for the determination of the crystallinity of polymorphic drugs. The selection of optimal spectral ranges that correlate with the lattice specificity and content specificity is crucial to obtaining a specific NIR model. In the present work, near-infrared （NIR） spectra of cefazolin sodium with different crystal forms created through different processes were studied. The results suggest that wavelengths within the range of 9102.7-8597.5 cm-1 is related to the specificity of the cefazolin sodium crystal lattice and that the range of 6001.6-5496.4 cm i is associated with the quantitative content of cefazolin sodium. The two ab- sorptions are caused by the second overtone of the C-H stretching band （3nC-H） and the first overtone of C-H stretching band （2uC-H）, respectively. Using these results, we established a suitable method of constructing a universal quantitative model by using mixed samples in different crystal forms as a calibration set, selecting a content-specific range （6001.6-5496.4 cm-l）, and adding lattice-related spectral ranges where appropriate. This may provide a framework for the construction of prediction models for polymorphic medicines.展开更多
One kind of new cefazolin sodium hydrate crystal was obtained in the isopropyl alcohol-water system.There are two symmetry independent molecules in the asymmetric unit,both being well ordered in the lattice,and ten in...One kind of new cefazolin sodium hydrate crystal was obtained in the isopropyl alcohol-water system.There are two symmetry independent molecules in the asymmetric unit,both being well ordered in the lattice,and ten independent water positions but generally four to six(mean five)water molecules and one sodium ion present in the unit cell structure.Huge solvent tunnels can be found.Again there are two general regions of water molecules,those in the large solvent tunnels and those in proximity of the sodium ion and the tetrazole moieties of the drug molecule.The physical and chemical characteristics of the new cefazolin sodium hydrate crystal are similar to that of the α-form cefazolin sodium crystal,and the new crystal has better chemical stability than amorphous cefazolin sodium powder.展开更多
文摘\ According to the analysis of the residual products by thermogravimetric analysis (TGA), the thermal decomposition process of cefazolin sodium (CEZ·Na) was thought to be similar to the degradation in solid state in its storage time. This laid a foundation for estimating the relative chemical stability of the drug by determination of its decomposition kinetics using TGA. Although the observed thermal decomposition kinetics of CEZ·Na was complex, a conversion level of 1% was chosen for evaluation of the stability of CEZ·Na crystalline since the mechanism here was more likely to be that of the actual product failure. The evaluation results suggested that the α form of CEZ·Na had the best stability and the amorphous one was the least stable one among α form, dehydrated α form and amorphous form.
基金National Natural Science Foundation(Grant No.81373372)Specialized Research Fund for the Doctoral Program of Higher Education of China(Grant No.20110001110021 and 20130001110059)
文摘A sensitive and specific high performance liquid chromatography method was established for measuring cefazolin sodium level in rabbit synovial fluid. Acetonitrile was used to precipitate proteins and antipyrine was used as internal standard. Samples were analyzed on a Dionex Ultimate U3000 HPLC system equipped with Phenomenex Luna C18 column （150 mmx4.60 mm, 5 Bm, 100 A）. The mobile phase consisted of acetonitrile and 0.1% formic acid in water. The flow rate was 1 mL/min. The detection wavelength was set at 272 nm. The column temperature was maintained at 25 ℃. The calibration curve was linear in the range of 1.0-100.0 μg/mL （r2 = 0.9999）. The limit of detection （LOD, S/N - 3） was 0.07 μg/mL. The limit of quantitation （LOD, S/N = 10） was 0.22 pg/mL. The recovery of cefazolin sodium （low, medium and high） was 124.6%, 117.8%, and 100.6% （RSD% - 1.9%, 4.0%, 1.1%, n = 5）, respectively. The intra-day and inter-day precision values were in the range of 0.5%-2.7%. The method was simple, sensitive and reliable. It can be used for the quantitative determination of cefazolin sodium in rabbit synovial fluid.
基金the National Key New Drug R&D Program Foundation of China (2010ZX09401-403) for the financial support
文摘Cefazolin sodium can form both α- and β-form crystals. It also can form dehydrated crystalline and amorphous products through different production processes. Because different polymorphic medicines usually have different physical and chemical properties, it is critical to emphasize the crystallization control of polymorphic medicines. Near-infrared （NIR） analysis, which incorporates a combination of NIR spectroscopic techniques and multivariate chemometric methods, is considered a powerful tool for the determination of the crystallinity of polymorphic drugs. The selection of optimal spectral ranges that correlate with the lattice specificity and content specificity is crucial to obtaining a specific NIR model. In the present work, near-infrared （NIR） spectra of cefazolin sodium with different crystal forms created through different processes were studied. The results suggest that wavelengths within the range of 9102.7-8597.5 cm-1 is related to the specificity of the cefazolin sodium crystal lattice and that the range of 6001.6-5496.4 cm i is associated with the quantitative content of cefazolin sodium. The two ab- sorptions are caused by the second overtone of the C-H stretching band （3nC-H） and the first overtone of C-H stretching band （2uC-H）, respectively. Using these results, we established a suitable method of constructing a universal quantitative model by using mixed samples in different crystal forms as a calibration set, selecting a content-specific range （6001.6-5496.4 cm-l）, and adding lattice-related spectral ranges where appropriate. This may provide a framework for the construction of prediction models for polymorphic medicines.
文摘One kind of new cefazolin sodium hydrate crystal was obtained in the isopropyl alcohol-water system.There are two symmetry independent molecules in the asymmetric unit,both being well ordered in the lattice,and ten independent water positions but generally four to six(mean five)water molecules and one sodium ion present in the unit cell structure.Huge solvent tunnels can be found.Again there are two general regions of water molecules,those in the large solvent tunnels and those in proximity of the sodium ion and the tetrazole moieties of the drug molecule.The physical and chemical characteristics of the new cefazolin sodium hydrate crystal are similar to that of the α-form cefazolin sodium crystal,and the new crystal has better chemical stability than amorphous cefazolin sodium powder.
