摘要
目的 优化硝酸甘油溶液及其制剂有关物质的测定方法。方法 更换现行标准2020年版《中国药典(二部)》高效液相色谱(HPLC)法中的流动相,采用梯度洗脱,并优化系统适用性溶液的制备方法。色谱柱为Ecosil 120-5-C18AQ柱(250 mm×4.6 mm,5μm),流动相为水-甲醇(梯度洗脱),流速为1.0 mL/min,检测波长为215 nm,柱温为30℃,进样量为20μL。结果 硝酸甘油的定量限和检测限分别为0.21μg/mL和0.07μg/mL。精密度、稳定性试验结果的RSD均小于2.0%。优化HPLC条件后成功分离了硝酸甘油与已知杂质2-硝酸甘油、1-硝酸甘油、1,3-二硝酸甘油、1,2-二硝酸甘油;明确了游离硝酸根扣除问题;参考British Pharmacopoeia2023并结合样品测定情况,拟订除硝酸根外,4个已知杂质均不得过0.5%,其余单个最大杂质溶液不得过0.1%、注射液和片剂不得过0.5%,杂质总量溶液和注射液不得过1.5%,、片剂不得过2.0%。结论 建立的方法准确、快速、专属性强,适用于硝酸甘油溶液及其制剂的有关物质检查,为加强本品的质量控制和进一步的质量标准修订提供参考。
Objective To optimize the determination method of related substances in nitroglycerin solution and its preparations.Methods The mobile phase in the high-performance liquid chromatography(HPLC)method of the current standard Chinese Pharmacopoeia(2020 Edition,VolumeⅡ)was replaced,the gradient elution method was adopted,and the preparation method of the system suitability solution was optimized.The chromatographic column was the Ecosil 120-5-C18 AQ column(250 mm×4.6 mm,5μm),the mobile phase was water-methanol(gradient elution),the flow rate was 1.0 mL/min,the detection wavelength was 215 nm,the column temperature was 30℃,and the injection volume was 20μL.Results The limit of quantification and limit of detection of nitroglycerin were 0.21μg/mL and 0.07μg/mL respectively.The RSDs of precision and stability tests were both lower than 2.0%.After optimization of the HPLC conditions,the nitroglycerin was successfully separated from the known impurities such as 2-glycerol mononitrate,1-glycerol mononitrate,1,3-glycerol dinitrate,1,2-glycerol dinitrate;the deduction of free nitrate ions was clarified;based on the British Pharmacopeia 2023 and the content determination of related substances in samples,it was proposed that all four known impurities should be not over 0.5%except for the nitrate ion,the other single maximum impurity should be not over 0.1%in the solution and 0.5%in the injection and tablets,the total amount of impurities should be not over 1.5%in the solution and injection and 2.0%in the tablets.Conclusion The established method is accurate,rapid,and specific,which is suitable for the inspection of related substances in nitroglycerin solution and its preparations.This study provides a reference for strengthening the quality control and further revision of the quality standards of this product.
作者
杨梅
李梓莹
伍良涌
李玮玲
董顺玲
YANG Mei;LI Ziying;WU Liangyong;LI Weiling;DONG Shunling(Guangzhou Institute for Drug Control,Guangzhou,Guangdong,China 510160)
出处
《中国药业》
CAS
2024年第18期82-86,共5页
China Pharmaceuticals
基金
国家药典委员会国家药品标准提高课题[2020H029,2020H030]。
