摘要
目的 通过不同pH的5％葡萄糖注射液与注射用两性霉素B配伍,以探讨5％葡萄糖注射液的pH变化对注射用两性霉素B的影响.方法 分别用盐酸(HCl)和氢氧化钠(NaOH)调节5％葡萄糖溶液至pH=3.2、3.4、3.6、3.8、4.0、4.2、4.4、4.6、4.8、5.0,并分别与注射用两性霉素B配伍,在避光条件下室温放置0、1、2、3、4、5、6、7 h.以高效液相色谱法测定两性霉素B的含量变化情况,同时考察供试液的pH变化情况;通过加速实验增加输液体系中两性霉素B降解产物量,并最终通过质谱分析来确定其化学结构.结果 pH ≤ 3.4的5％葡萄糖注射液与注射用两性霉素B配伍后会产生明显可见的浑浊沉淀;5％葡萄糖注射液pH≤4时,随着放置时间的延长,注射用两性霉素B相对含量下降,降解量可达10％,而降解到的杂质结构为甲氧基取代杂质.结论 为了保证注射用两性霉素B的输液安全,在溶媒pH符合要求的前提下,减少输液时间可以有效降低两性霉素B的降解.
Abstract
Objective To investigate the effect of pH change of 5％glucose injection on amphotericin B for injection through the compatibility of amphotericin B for injection with 5％glucose injection at different pH.Methods 5％glucose solution was adjusted to pH=3.2,3.4,3.6,3.8,4.0,4.2,4.4,4.6,4.8,5.0 with hydrochloric acid(HCl)and sodium hydroxide(NaOH),respectively,and then mixed with amphotericin B for injection.Amphotericin B was placed at room temperature for 0,1,2,3,4,5,6,7 h under dark conditions.The content of amphotericin B was determined by high performance liquid chromatography,and the pH changes of the test solution were investigated;the amount of amphotericin B degradation products in the infusion system was increased by accelerated experiments,finally,its chemical structure was determined by mass spectrometry.Results After the compatibility of 5％glucose injection with amphotericin B for injection at pH ≤ 3.4,there will be obvious visible turbidity precipitation;when the pH of 5％glucose injection was ≤ 4,the relative content of amphotericin B for injection decreased with the extension of storage time,and the degradation amount can reach 10％,while the degraded impurity structure was methoxy substitution impurity.Conclusion In order to ensure the safety of amphotericin B for injection,reducing the infusion time can effectively reduce the degradation of amphotericin B under the premise that the pH of the solvent meets the requirements.
维普
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