2015年版《中国药典》环磷酰胺有关物质检测方法的验证与改进
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摘要
目的:改进环磷酰胺有关物质的检测方法。方法:对2015年版《中国药典》收载的环磷酰胺有关物质检测的薄层色谱法(TLC)进行验证,并对该方法进行改进,以环磷酰胺有关物质A、B、C、D对照品为对照,以二氯甲烷-冰乙酸-甲醇-水(50∶25∶15∶12,V/V/V/V)为展开剂,以茚三酮试液为显色剂,进行有关物质检测试验及方法学验证。结果:原TLC法不仅无法检测到环磷酰胺有关物质B、C、D,且操作过程烦琐,不够环保。改进后的TLC法对环磷酰胺有关物质A的检测限约为0.05μg,对有关物质B、C、D的检测限约为0.1μg;方法专属性试验结果表明,环磷酰胺与各有关物质之间互不干扰,分离度良好。结论:改进的TLC法具有简便、环保、灵敏度高的优点,可用于环磷酰胺及其制剂的质量控制。
OBJECTIVE:To improve the detection method for the related substances of cyclophosphamide. METHODS:The TLC for the detection method of the cyclophosphamide related substances in Chinese Pharmacopoeia(2015 edition)was verified;the TLC was improved with references of compound A,B,C,D,the expanding agent of dichloromethane-acetic acid-methanol-water(50:25:15:12,V/V/V/V)and the chromogenic agent of ninhydrin solution,and the detection test and methodology validation were conducted for the related substances. RESULTS:The original TLC can not detect the cyclophosphamide related compound B,C,D,and the operation process was cumbersome and not environmental protection. The detection limit of improved TLC for cyclophosphamide related compound A was 0.05 μg,and 0.1 μg for related compound B,C,D;specificity method test results showed that cyclophosphamide and the related compounds did not interfere with each other with a good separation. CONCLUSIONS:Improved TLC has the advantages of simplicity,environmental protection and high sensitivity,which can be used for the quality control of cyclophosphamide and its preparations.
OBJECTIVE:To improve the detection method for the related substances of cyclophosphamide. METHODS:The TLC for the detection method of the cyclophosphamide related substances in Chinese Pharmacopoeia(2015 edition)was verified;the TLC was improved with references of compound A,B,C,D,the expanding agent of dichloromethane-acetic acid-methanol-water(50:25:15:12,V/V/V/V)and the chromogenic agent of ninhydrin solution,and the detection test and methodology validation were conducted for the related substances. RESULTS:The original TLC can not detect the cyclophosphamide related compound B,C,D,and the operation process was cumbersome and not environmental protection. The detection limit of improved TLC for cyclophosphamide related compound A was 0.05 μg,and 0.1 μg for related compound B,C,D;specificity method test results showed that cyclophosphamide and the related compounds did not interfere with each other with a good separation. CONCLUSIONS:Improved TLC has the advantages of simplicity,environmental protection and high sensitivity,which can be used for the quality control of cyclophosphamide and its preparations.
引文
[1]国家药典委员会.中华人民共和国药典:二部药典注释[S].1990:310.
[2]国家药典委员会.中华人民共和国药典:二部[S].2015年版.北京:中国医药科技出版社,2015:586.
[3]袁红露.环磷酰胺原料药中有关物质的分析方法[D].杭州:浙江大学,2014.
[4]王淼,梁蔚阳.高效液相色谱法测定注射用环磷酰胺的有关物质和降解产物[J].中国生化药物杂志,2008,29(4):275.
[5]梁云爱,李见春,门孝英.环磷酰胺及其制剂的二阶导数差示脉冲极谱法定量研究[J].中国药学杂志,2001,36(9):620.
[6]卞晓岚,翟青.HPLC法测定复方环磷酰胺胶囊中环磷酰胺的含量[J].广东药学院学报,2004,20(5):491.
[7]刘澄凡,韩远乐,赵强,等.环磷酰胺的示波极谱法测定[J].分析测试学报,1994,13(5):48.
[8]王文辉,杨俊,陈瑶,等.超高效液相色谱-质谱法测定人体血浆中的环磷酰胺[J].光谱实验室,2011,28(6):2 887.
[9]王燕琼,张顺国,徐涛,等.环磷酰胺注射液在玻璃瓶和PVC软输液袋中的稳定性考察[J].药学实践杂志,2010,28(5):361.
[2]国家药典委员会.中华人民共和国药典:二部[S].2015年版.北京:中国医药科技出版社,2015:586.
[3]袁红露.环磷酰胺原料药中有关物质的分析方法[D].杭州:浙江大学,2014.
[4]王淼,梁蔚阳.高效液相色谱法测定注射用环磷酰胺的有关物质和降解产物[J].中国生化药物杂志,2008,29(4):275.
[5]梁云爱,李见春,门孝英.环磷酰胺及其制剂的二阶导数差示脉冲极谱法定量研究[J].中国药学杂志,2001,36(9):620.
[6]卞晓岚,翟青.HPLC法测定复方环磷酰胺胶囊中环磷酰胺的含量[J].广东药学院学报,2004,20(5):491.
[7]刘澄凡,韩远乐,赵强,等.环磷酰胺的示波极谱法测定[J].分析测试学报,1994,13(5):48.
[8]王文辉,杨俊,陈瑶,等.超高效液相色谱-质谱法测定人体血浆中的环磷酰胺[J].光谱实验室,2011,28(6):2 887.
[9]王燕琼,张顺国,徐涛,等.环磷酰胺注射液在玻璃瓶和PVC软输液袋中的稳定性考察[J].药学实践杂志,2010,28(5):361.