不同pH的5%葡萄糖注射液与注射用两性霉素B配伍的稳定性研究

Study on the compatbility stability of amphotericin B for injection in 5%glucose injection with different pH

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臆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臆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。

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.