不同溶解方法对环磷酰胺药效影响的观察

A study on effect of different dissolved methods on cyclophosphamide

目的：观察采用振荡和加温两种方法溶解环磷酰胺粉针剂时,在保证药效的前提下使其完全溶解的振荡时间及温度。方法：振荡溶解法：将3种不同批号的环磷酰胺西林瓶（每支200 mg）中各注入10 mL 0.9%NaCl,放在同一个振荡器上进行振荡,分别在振荡后的1、2、4、6、8、15 min取出,采用高效液相仪测定每个时间点的药物含量,进而确定振荡的时间。加温溶解法：将3种不同批号的环磷酰胺西林瓶（每支200 mg）中各注入10mL 0.9%NaCl,放入不同温度（37、50、60、65℃）的恒温箱中加温,分别在每个温度点下的1、2、4、6、8、15 min时取出,采用高效液相仪测定各时间点的药物含量,进而确定药物溶解的最佳温度。结果：加温溶解法：37℃下环磷酰胺的溶解时间为1 5 min时,含量为（94.69±1.11）%;50和60℃下环磷酰胺在溶解时间达6 min时,含量分别为（95.27±1.58）%和（97.74±0.80）%,超过6 min后,含量明显下降;在65℃时环磷酰胺在溶解时间达4 min时含量即可达（95.46±1.09）%,但其在15 min时下降至约87%。振荡溶解法：环磷酰胺完全溶解最短时间为8 min,含量为（96.09±1.67）%。结论：采用振荡溶解法环磷酰胺完全溶解的最短时间为8 min。配制环磷酰胺时温度以50~60℃为宜,时间为6 min。

Objective： To explore the optimal oscillating times and heating temperatures in dissolving cyclophosphamide powder.Methods： We chose three different batches of cyclophosphamide（200mg per vial）,injected 10ml 0.9% NaCl solution,Then dissolved the drug powder in two different methods followed：in the oscillametric method group（OMG）,put the vials in the oscillator and measured the drug content using high performance liquid chromatography at 1,2,4,6,8,15 minutes respectively,in order to determine the optimal required time;in the heating method group（HMG）,heated the vials for different temperature（37℃,50℃,60℃ and 65℃）and measured the drug content after 1,2,4,6,8,15 minutes respectively,inorder to determine the optimal temperature.Results： In the HMG,the required time was 15 minutes in the temperature of 37℃ with the drug content（94.69±1.11）%,and the required time was 6 minutes in the temperature of 50℃ and 60℃,with the drug contents（95.27±1.58）% and（97.74±0.80）% respectively.After 6 min,the drug content was significantly decreased.At 65℃,the drug content was（95.46±1.09）% at 4 minutes,then decreased to 87% at 15 minutes.In the OMG,the optimal time for complete dissolution was 8 minutes with the drug content（96.09±1.67）%.Conclusion：The optimal time for complete dissolution of cyclophosphamide is 8 minutes in the oscillametric method,and the optimal temperature is 50～60℃ for 6 minutes in the heating method.