甘草酸二铵磷脂复合物注射剂中溶血磷脂酰胆碱的稳定性研究

Stability investigation on lysophosphatidylcholine in the diammonium glycyrrhizinate phospholipid complex injections

目的：采用高效液相色谱-蒸发光散射检测器法（HPLC-ELSD）测定甘草酸二铵磷脂复合物（DGPC）及其注射液中溶血磷脂酰胆碱（LPC）的含量变化。方法：制备3种不同类型的甘草酸二铵磷脂复合物注射剂（小针剂：规格0.2g∶10mL;5%木糖醇输液：规格0.2g∶50mL;5%葡萄糖输液：规格0.2g∶50mL）,并在40℃下进行加速试验。采用Alltima硅胶柱（5μm,4.6mm×150mm）为色谱柱,流动相为甲醇-冰醋酸（500∶10,三乙胺调p H至6.0）,流速1.2mL·min^-1;蒸发光散射检测器的漂移管温度85℃,氮气为载气,流量为1.6L·min^-1。用标准曲线法计算溶血磷脂酰胆碱的含量,以峰面积和浓度的双对数拟合方程。结果：在选定检测条件下,磷脂酰胆碱和溶血磷脂酰胆碱的分离度良好。测定结果显示,注射剂加速实验过程中溶血磷脂酰胆碱的含量基本稳定,3种注射剂溶血磷脂酰胆碱质量浓度分别波动在0.96～1.06、0.25～0.32、0.20～0.26mg·mL^-1。结论：甘草酸二铵磷脂复合物注射液在加速实验中溶血磷脂酰胆碱的限量符合含磷脂的脂肪乳类静脉制剂的药品标准。

Objective： To determine the changes in the content of lysophosphatidylcholine（ LPC） in the diammonium glycyrrhizinate phospholipid complex（ DGPC） and its injections by HPLC- ELSD.Methods： Three types of diammonium glycyrrhizinate phospholipid complex injections were prepared（ small volume injection： 0.2g∶10mL;5% xylitol infusion： 0.2g∶50mL; 5% glucose infusion： 0.2 g∶50mL） and underwent acceleration test at 40 ℃.An Alltima Silica column（ 5μm,4.6mm×150mm） was used for the HPLC method.The mobile phase was methanol- glacialacetic acid（ 500∶10,adjusted p H 6.0 with triethylamine） with a flow rate of 1.2mL·min^-1.The drift tube temperature of ELSD was maintained at 85℃ and the flow rate of nitrogen gas was kept at 1.6 L·min^-1.The contents of LPC were calculated by standard curve,with double logarithmic equation of peak area and drug concentration.Results： Under the selected conditions,phosphatidylcholine and lysophosphatidylcholine had a good separation.The results showed the contents of lysophosphatidylcholine in the injections were stable throughout the acceleration test.The contents in the three types of injections were fluctuated between 0.96- 1.06 mg·mL^-1,0.25-0.32 mg·mL^-1,0.20-0.26 mg·mL^-1,respectively.Conclusion： The contents of lysophosphatidylcholine in diammonium glycyrrhizinate phospholipid complex injections meet the drug standard of fat emulsion containing phospholipid in the acceleration study.