冷藏药品尼可地尔与不同载体溶媒配伍后的稳定性研究

Study on stability of refrigerated drug Nicorandil compatible with solvents of different carriers

目的研究冷藏药品尼可地尔与不同载体溶媒配伍后溶液的稳定性。方法尼可地尔用0.9%氯化钠注射液或5%葡萄糖注射液溶解,分别于室温或冷藏放置8 h;采用超高效液相色谱法测量尼可地尔浓度的变化,色谱条件:色谱柱ACE-C_(18)(50 mm×2.1 mm,2.5μm),柱温40℃,流动相甲醇-水(42∶58),流速0.4 mL/min,检测波长254 nm;用pH计测量溶液pH的变化;用微粒分析仪测量微粒数目变化。结果尼可地尔的线性范围为3.316～18.896 mg/L(r=0.999),尼可地尔与不同载体溶媒配伍并在不同温度保存条件下, 8 h内药物浓度和pH值变化不明显;≥25μm的微粒数目正常,≥10μm的微粒数目较大。结论尼可地尔与不同载体溶媒配伍溶液在室温和冷藏条件下8 h内稳定性良好,但≥10μm的微粒数目超过规定。

Objective To study the stability of refrigerated drug Nicorandil compatible with solvents of different carriers.Methods The solutions of nicorandil dissolved with 0.9%sodium chloride injection or 5%glucose Injection were stored at room temperature or low temperature for 8 h.The concentration of nicorandil was determined by ultra-high performance liquid chromatography,and the chromatographic conditions were as follows:chromatographic column was ACE-C 18(50 mm×2.1 mm,2.5μm)column and the column temperature was 40℃,the mobile phase was methanol-water(42∶58)with a flow rate of 0.4 mL/min,the detection wavelength was set at 254 nm.The changes of pH were measured with pH meter.The number of insoluble particles were surveyed by particle analyzer.Results The linear ranges of nicorandil was 3.316-18.896 mg/L(r=0.999).The concentration of nicorandil and the value of pH were stable after dissolved in different solvents and stored at different temperatures within 8 h.Additionally,the amount of particles(≥25μm)was normal,while amount of particles(≥10μm)was relatively larger.Conclusion When stored at either room temperature or low temperature,the stability of nicorandil solution after dissolved in different solvents is desirable within 8 h,while the amount of particles(≥10μm)exceed the number of regulation.