HPLC柱前衍生化法测定药用辅料中甲醛、乙醛时空白干扰的探索及方法优化  

Research on blank interference and method optimization for determination of formaldehyde and aldehyde in pharmaceutical excipients by HPLC with pre-column derivatization

作　　者：江颖 王珏[1] 许凯 杨锐[1] 孙会敏[1] JIANG Ying;WANG Jue;XU Kai;YANG Rui;SUN Hui-min(NMPA Key Laboratory for Quality Research and Evaluation of Pharmaceutical Excipients,National Institutes for Food and Drug Control,Beijing 100050,China)

机构地区：[1]国家药品监督管理局药用辅料质量研究与评价重点实验室,中国食品药品检定研究院,北京100050

出　　处：《药物分析杂志》2020年第11期2062-2069,共8页Chinese Journal of Pharmaceutical Analysis

基　　金：国家科技重大专项资助项目(2017ZX09101001006)。

摘　　要：目的:探究HPLC柱前衍生化法测定药用辅料中甲醛、乙醛时空白干扰的来源,并建立方法消除干扰,优化甲醛、乙醛的测定方法。方法:采用高效液相色谱法结合影响因素实验初步判断各可能来源对空白干扰的贡献程度,并采用GC-MS法对实验使用的溶剂及流动相中甲醛、乙醛杂质进行定量,采用乙腈重结晶法对衍生化试剂2,4-二硝基苯肼进行纯化以去除空白中的干扰杂质(甲醛2,4-二硝基苯腙、乙醛2、4-二硝基苯腙)。结果:2,4-二硝基苯肼是甲醛、乙醛测定中空白干扰的主要来源,溶剂及流动相对空白干扰的影响可忽略不计。结论:不同来源的2,4-二硝基苯肼经乙腈重结晶后,2种干扰杂质均未检出。采用乙腈对2,4-二硝基苯肼进行纯化可有效消除空白干扰,实现方法的优化。Objective:To explore the source of blank interference in the determination of formaldehyde and acetaldehyde in pharmaceutical excipients by HPLC with pre-column derivatization,and to establish a method to remove the blank interference and optimize the determination of formaldehyde and acetaldehyde.Methods:High performance liquid chromatography(HPLC)combined with influencing factors experiment was used to preliminarily determine the contribution of various possible sources of the blank interference.The formaldehyde and acetaldehyde impurities in the experimental solvents and mobile phases were quantified by GC-MS.2,4-dinitrophenylhydrazine was purified by acetonitrile recrystallization to remove the interfering impurities(formaldehyde-DNPH,acetaldehyde-DNPH)in blank.Results:2,4-dinitrophenylhydrazine was the main source of blank interference in the determination of formaldehyde and acetaldehyde,and the influence of solvent and mobile phase on blank interference was negligible.Conclusion:After recrystallization of 2,4-dinitrophenylhydrazine from different sources with acetonitrile,no interference impurities are detected.Purification of 2,4-dinitrophenylhydrazine with acetonitrile could effectively eliminate the blank interference and optimize the method.

关 键 词：药用辅料 甲醛 乙醛 空白干扰 2 4-二硝基苯肼 方法优化 

分 类 号：R917[医药卫生—药物分析学]