原淀粉和改性淀粉中的硝酸盐与亚硝酸盐考察研究及风险探讨  

Research on determination and risk discussion of nitrate and nitrite in native starch and modified starch

作　　者：胡淑君 陈英[1] 余少文[1] 李艺 王淼[1] 叶秀金[1] 王彩媚[1] HU Shu-jun;CHEN Ying;YU Shao-wen;LI Yi;WANG Miao;YE Xiu-jin;WANG Cai-mei(Guangdong Institute for Drug Control,NMPA Key Laboratory for Quality Control and Evaluation of Pharmaceutical Excipients,Guangzhou 510663,China)

机构地区：[1]广东省药品检验所国家药品监督管理局药用辅料质量控制与评价重点实验室,广州510663

出　　处：《药物分析杂志》2025年第2期297-303,共7页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:通过考察原淀粉和改性淀粉类药用辅料中的硝酸盐和亚硝酸盐,来探讨辅料对药品中亚硝胺类杂质形成的影响。方法:采用离子色谱法测定硝酸盐和亚硝酸盐的含量。采用Dionex IonPac AS11-HC(4μm,2 mm×250 mm)色谱柱,电导检测器,抑制电导检测,流动相为0.015 mol·L^(-1)氢氧化钾溶液,流速为1.0 mL·min^(-1),柱温为30℃,进样体积为25μL。对方法的专属性、线性、检测限和定量限、精密度、准确度和耐用性进行了验证。结果:对9种共119批原淀粉和改性淀粉样品进行了测定,硝酸盐在所有38批原淀粉中均有检出,含量为1~70μg·g^(-1);在55批(共81批)改性淀粉中也有检出,含量为2~1110μg·g^(-1),其中糊精的硝酸盐含量最高。亚硝酸盐在33批原淀粉中有检出,含量为0.3~2.5μg·g^(-1);在17批改性淀粉中有检出,含量为1.1~13.0μg·g^(-1)。结论该方法经验证,适用于测定淀粉类药用辅料中的硝酸盐和亚硝酸盐。辅料中的硝酸盐和亚硝酸盐控制是药物制剂亚硝胺杂质风险控制的一个重要部分,应给予充分重视。Objective:To discuss the influence of the pharmaceutical excipients on the nitrosamine formation in drugs by studying the nitrate and nitrite in native starch and modified starch.Methods:A methodologyfor the determination of nitrate and nitrite in starch was developed by ion chromatography with a suppressed conductivity detector.A Dionex IonPac anion-exchange column(AS11-HC,4 mm,2×250 mm)at a temperature of 30℃was utilized.An electrolytically generated potassium hydroxide solution with a concentration of 0.015 mL·L^(-1)was delivered at a rate of 1.0 mL·min^(-1).The injection volume was 25μL.The method was validated in terms of specificity,linearity,LOD&LOQ,precision,accuracy and robustness.Results:119 samples from 9 different categories of native starch and modified starch were analyzed.Nitrate was detected in all 38 samples of native starch in a range of 1-70μg'g',and identified in 55 out of 81 samples of modified starch in a range of 2-1110μg·g^(-1),Among the modified starch samples,dextrin had the maximum concentration of nitrate.Similarly,nitrite was detected in 33 out of 38 samples of native starch in a range of 0.3-2.5μg·g^(-1),and 17 out of 81 samples of modified starch in a range of 1.1-13.0μg·g^(-1).Conclusion:This method has been proven to be suitable for determining the nitrate and nitrite in starch based pharmaceutical excipients.The controlling of nitrate and nitrite in the pharmaceutical excipients is an important part of the nitrosamine risk control in the drugs and should be given sufficient attention.

关 键 词：原淀粉 改性淀粉 药用辅料 硝酸盐 亚硝酸盐 亚硝胺 风险 

分 类 号：R917[医药卫生—药物分析学]