| A subtained-rlease injection of Cefquinome Sulfate (CEF) was prepared by suspending the CEF in soybean oil and ethyl oleate. After testing the disperse medium, suspending agent, wetting agent and oxidation inhibitor, the optimized formulation was gained through determining the total score of settling volume ratio and redispersibility as the index. Orthogonal design experiment was used to investigate the formulation and technology,then an optimized formulation and technology was successfully obtained. Trough carrying quality evaluation, safety, and validity test, The result shows the preparation is safe, effective and under-controlling.A HPLC-UV method was developed for the determination of CEF ranging from0.05to20.0μg/mL in pig plasma with a good linear relationship (R2=0.9999). The limit of detection(LOD) and quantification(LOQ) of CEF in pig plasma were0.015μg/mL and0.05μg/mL,respectively.The recoveries for CEF at added levels of0.05,5.0and20.0μg/mL were89.85%,90.43%,92.54%, respectively;the intra-day coefficiences of variation were3.65%,2.73%,3.22%; and the inter-day coefficiences of variation were4.18%,3.57%,3.69%.A HPLC-UV method was developed for the determination of CEF ranging from0.05to20.0μg/mL in dairy cow plasma with a good linear relationship (R2=0.9998). The LOD and LOQ of CEF in dairy cow plasma were0.015μg/mL and0.05μg/mL, respectively.The recoveries for CEF at added levels of0.05,5.0and20.0μg/mL were86.30%,89.02%,91.41%,respectively;the intra-day coefficiences of variation were4.14%,5.26%,6.08%; and the inter-day coefficiences of variation were5.69%,6.35%,5.10%.In pharmacokinetic tests, the CEF concentrations of pig and dairy cow plasma were determined by HPLC-UV after intramuscular administration CEF subtained-release injection and COBACTAN CEF suspension injection, the pharmacokinetic parameters were calculated with DAS2.1.1analysis software. The results showed the peak time were2.75h and0.98h;the peak concentrations were3.02μg/mL and3.68ug/mL;the elimination half lives were6.56h and3.74h;the blood drug concentration(0.01μg/mL) were kept36-48h and12-24h,respectively in pigs; the peak time were2.25h and1.92h; the peak concentrations were2.87μg/mL and3.79μg/mL; the elimination half lives were10.54h and2.14h;the blood drug concentration(0.01μg/mL) were kept36-48h and24-36h in dairy cows.The results showed the preparation has sustained-release effect, the pharmacokinetics parameters of CEF sustained-release injection were improved than COBACTAN CEF suspension injection.In vitro pharmacodynamics test,the results showed antibacterial activity of cefquinome sulfate sustained-release injection were strong on Escherichia coli, Staphylococcus aureus, Actinobacillus pleuropneumoniae and pasteurella multocida.after the pigs were infected Escherichia coli artificially,following intramuscular administration once daily at a dose of2mg/kg body weight for three days, the cure rate was80%, the effective rate was90%.CEF sustained-release injection were injected intramuscularly with1mg/kg body weight doses to mastitis bovine,1time a day, for3days, the cure rate was90%and the efficiency was90%, The results indicated that this preparation has a good effect on swine Escherichia coli disease and dairy cow mastitis at recommended doses.A HPLC-UV method was developed for the determination of CEF ranging from0.01to10.0μg/mL in milk with a good linear relationship (R2=0.9999). The LOD and LOQ of CEF in milk were0.006μg/mL and0.02μg/mL, respectively.The recoveries for CEF at added levels of0.05,0.50and5.00μg/mL were88.69%,90.80%,91.47%, respectively; the intra-day coefficiences of variation were4.13%,4.95%,5.26%, and the inter-day coefficiences of variation were5.45%,5.83%,6.71%.The method was simple, rapid and effective, which can be used for the detection of CEF in milk.The results showed that CEF concentration reached the highest value in12-24h in dairy milk. The drug was not detected at96h. So the milk withdraw time of the preparation was advised as4days. |
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