注射用脂溶性维生素(Ⅱ)/水溶性维生素与常用电解质配伍的稳定性考察

Compatibility Stability Investigation of Fat-soluble Vitamin(Ⅱ)/Water-soluble Vitamin for Injection with Common Electrolytes

目的:考察注射用脂溶性维生素(Ⅱ)/水溶性维生素与常用电解质的配伍稳定性。方法:参考临床常用剂量,取注射用脂溶性维生素(Ⅱ)/水溶性维生素组合包装[含注射用脂溶性维生素(Ⅱ)2瓶和注射用水溶性维生素1瓶]分别与葡萄糖注射液、氯化钾注射液、浓氯化钠注射液、碳酸氢钠注射液、门冬氨酸钾注射液、门冬氨酸钾镁注射液、甘油磷酸钠注射液、多种微量元素注射液(Ⅱ)配伍,得配伍液A^H。在室温(25℃)下,分别于0、1、2、3、4 h时考察各配伍液的外观、p H值、渗透压摩尔浓度和不溶性微粒数,并于0、4 h时检查其细菌内毒素含量。结果:配制后4 h内,各配伍液外观无明显变化;配伍液H的p H值变化较大(RSD=5.13%,n=5),配伍液D和配伍液G的p H值明显升高;各配伍液的渗透压摩尔浓度均无明显变化(RSD<2%,n=5),且小于600m Osmol/kg;各配伍液细菌内毒素检查结果均为阴性。配制后2、4 h时,配伍液B中≥10μm的微粒数明显增加;配制后2、3、4 h时,配伍液E、F、H中≥10μm的微粒数明显增加;配制后0、1、2、3、4 h时,配伍液G中≥10μm的微粒数明显增加;上述配伍液中≥10μm的微粒数与同时间点的配伍液A比较,差异均有统计学意义(P<0.05),但均符合2015年版药典标准。配制后1、2、3、4 h时,配伍液D中≥10μm的微粒数明显增加,与同时间点的配伍液A比较,差异均有统计学意义(P<0.05);且配制后2、3、4 h时≥10μm的微粒数均超出药典规定范围。配制后4 h内,配伍液C中≥10μm的微粒数和各配伍液中≥25μm的微粒数均无明显变化,且符合药典标准。结论:由于p H值和不溶性微粒数变化较大,注射用脂溶性维生素(Ⅱ)/水溶性维生素不宜与多种微量元素注射液(Ⅱ)、甘油磷酸钠注射液或碳酸氢钠注射液配伍使用。

OBJECTIVE:To investigate the compatibility stability of Fat-soluble vitamin(Ⅱ)/Water-soluble vitamin for injection with common electrolytes.METHODS:Referring to clinical common dose,Fat-soluble vitamin(Ⅱ)for injection/Water-soluble vitamin for injection collective packing[containing Fat-soluble vitamin(Ⅱ)for injection2ampoules and Water-soluble for injection1ampoule]were respectively mixed with Glucose injection,Potassium chloride injection,Concentrated sodium chlorideinjection,Sodium bicarbonate injection,Potassium aspartate injection,Potassium aspartate and magnesium aspartate injection,Sodium glycerophosphate injection,Multi-trace elements injection(Ⅱ)to obtain mixture A-H.At room temperature(25℃),these mixtures were investigated in terms of appearance,pH value,osmotic pressure molar concentration and the number of insoluble particles at0,1,2,3,4h.The contents of bacterial endotoxin were tested at0,4h.RESULTS:Within4h after mixing,there was no significant change in appearance of those mixtures;pH value of mixture H changed greatly(RSD=5.13%,n=5),and that of mixture D and G increased significantly.The osmotic pressure molar concentration of those mixtures had no significantly change(RSD<2%,n=5)and lower than600mOsmol/kg.The bacterial endotoxin tests of those mixtures were negative.Two andfour hours after mixing,the number of insoluble particles≥10μm in mixture B was increased significantly;2,3,4h after mixing,the number of insoluble particles≥10μm in mixture E,F,H were increased significantly;0,1,2,3,4h after mixing,thenumber of insoluble particles≥10μm in mixture G was increased significantly.There was statistical significance in the number ofinsoluble particle≥10μm in above mixtures compared to mixture A at the same time point(P<0.05),but it was in line with thestandard of2015pharmacopeia.One,two,three and four hours after mixing,the number of insoluble particle≥10μm in mixtureD was increased significantly,there was statistical significance compared to mixture A at the same time point(P<0.05);the numberof insoluble particle≥10μm in mixture D was beyond prescribed scope of pharmacopeia at2,3,4h after mixing.Within4hafter mixing,both the number of insoluble particle≥10μm in mixture C and the number of insoluble particle≥25μm in edch mixture had no significant change,in accordance with pharmacopeia standard.CONCLUSIONS:Fat-soluble vitamin(Ⅱ)/Water-soluble vitamin for injection is not suitable for mixing with Multi-trace elements injection(Ⅱ),Sodium glycerophosphate injection or Sodium bicarbonate injection due to great change of pH value and the number of insoluble particles.