注射用替加环素的制备、质量控制及稳定性考察

Preparation,Quality Control and Stability Study for Tigecycline for Injection

目的:制备注射用替加环素,并建立其质量控制方法及考察其稳定性。方法:筛选制备条件、辅料和中间体溶液的pH值,确定注射用替加环素的制备工艺和处方组成;采用高效液相色谱法测定其含量及有关物质,并对制剂进行稳定性考察(影响因素、加速试验和长期留样试验(24个月))。结果:制备条件以2～8℃为宜,处方中选用乳糖为赋形剂,其与主药用量比为2:1,中间体溶液的pH以7·5～8·5为宜;替加环素进样量线性范围为0·103～10·30μg(r=0·9999,n=7);低、中、高浓度平均回收率为99·9%、100·2%、100·2%,RSD=1·20%、0·50%、0·72%。稳定性考察期内各指标未见明显变化。结论:该制剂处方工艺可行,质量可控,稳定性较好。

OBJECTIVE：To prepare Tigecycline for injection,establish its quality control method and investigate its stability.METHODS：The preparation condition,excipients and pH value of intermediate solution were selected to confirm the preparation technology and formulation.The contents of tigecycline and related substance were determined by HPLC.Meanwhile,its stabilities of influencing factors,accelerated test and long-term（24 months） sample observation test were investigated.RESULTS：The preparation temperature was maintained within 2～8 ℃,and lactose was used as excipient,ratio of which to main component was 2：1.pH value of intermediate solution was 7.5～8.5.The linear range of tigecycline was 0.103～10.30 μg（r=0.999 9,n=7）.The average recovery rates of low,medium,high concentration were 99.9%,100.2% and 100.2%,RSD=1.20%,0.50% and 0.72%,respectively.No obvious changes were observed in each index of stability test.CONCLUSION：The preparation is feasible in technology,controllable and stable in quality.