高效液相色谱法检测对乙酰氨基酚片中有关物质  

Determination of Related Substances in Paracetamol Tablets by HPLC

作　　者：肖江 王辉 帅海涛 章泽恒[3] 黄致远 XIAO Jiang;WANG Hui;SHUAI Haitao;ZHANG Zeheng;HUANG Zhiyuan(Hunan Pharmaceutical Excipients Engineering and Technology Research Center Co.,Ltd.,Changsha,Hunan,China 410331;National Engineering and Technology Research Center of Pharmaceutical Excipients,Changsha,Hunan,China 410331;Hunan Drug Evaluation and Certification and Adverse Reaction Monitoring Center,Changsha,Hunan,China 410013)

机构地区：[1]湖南省药用辅料工程技术研究中心有限公司,湖南长沙410331 [2]国家药用辅料工程技术研究中心,湖南长沙410331 [3]湖南省药品审评认证与不良反应监测中心,湖南长沙410013

出　　处：《中国药业》2022年第21期55-59,共5页China Pharmaceuticals

基　　金：湖南省自然科学基金[2020JJ9004]。

摘　　要：目的建立测定对乙酰氨基酚片中对氨基酚、对氯苯乙酰胺、杂质A-I和杂质L-N 14个有关物质含量的高效液相色谱法。方法色谱柱为Xbridge C_(18)柱(250 mm×4.6 mm,5μm),流动相为0.1%冰醋酸水溶液-甲醇(梯度洗脱),流速为0.8 mL/min,柱温为30℃,检测波长为254 nm,进样量为5μL。结果杂质A-I与杂质L-N的相对校正因子分别为1.15,1.27,1.26,1.48,2.79,1.24,0.97,1.33,1.27,1.84,2.13,1.02。对乙酰氨基酚与14个有关物质色谱峰的分离度良好。14个有关物质的质量浓度均在各自的线性范围内与峰面积线性关系良好(R2>0.9990);检测限为0.02~0.11μg/mL,定量限为0.07~0.34μg/mL;中间精密度、稳定性、重复性试验的RSD均小于4.0%;平均加样回收率为98.74%~100.29%,RSD为0.26%~1.30%(n=9)。12批不同厂家的样品中14个有关物质含量为0.0080%~0.0704%,均检出对氨基酚、杂质A-D、杂质F、杂质H、杂质L、杂质N,均未检出对氯苯乙酰胺、杂质E、杂质G、杂质I、杂质M。结论该方法操作简便、专属性强、灵敏度和准确度均高,可用于对乙酰氨基酚片中有关物质的含量测定。Objective To establish a high-performance liquid chromatography(HPLC)method for the content determination of 14 related substances in Paracetamol Tablets,including p-aminophenol,p-chloroacetanilide,impurities A-I and impurities L-N.Methods The chromatographic column was Xbridge C_(18) column(250 mm×4.6 mm,5μm),the mobile phase was 0.1%acetic acid aqueous solution-methanol(gradient elution),the flow rate was 0.8 mL/min,the column temperature was 30℃,the detection wavelength was 254 nm,and the injection volume was 5μL.Results The relative correction factors(RCFs)of impurities A-I and impurities L-N were 1.15,1.27,1.26,1.48,2.79,1.24,0.97,1.33,1.27,1.84,2.13 and 1.02,respectively.The chromatographic peaks of paracetamol and 14 related substances were well separated.The 14 related substances had a good linear relationship with the peak area within their respective mass concentration range(R2>0.9990).The limit of detection(LOD)of the above 14 related substances was in the range of 0.02-0.11μg/mL,and their limit of quantitation(LOQ)was in the range of 0.07-0.34μg/mL.The RSDs of intermediate precision,stability and repeatability tests were all lower than 4.0%.The average recovery of the above 14 related substances was in the range of 98.74%-100.29%,and the RSD was in the range of 0.26%-1.30%(n=9).The content of 14 related substances in 12 batches samples from different manufacturers was in the range of 0.0080%-0.0704%,and p-aminophenol,impurities A-D,impurity F,impurity H,impurity L and impurity N were all detected in the above samples,while p-chloroacetanilide,impurity E,impurity G,impurity I and impurity M were all not detected in the above samples.Conclusion The method is simple,specific,sensitive and accurate,which can be used for the content determination of related substances in Paracetamol Tablets.

关 键 词：高效液相色谱法 对乙酰氨基酚片 有关物质 自身对照法 

分 类 号：R917[医药卫生—药物分析学] R971[医药卫生—药学]