摘要
目的建立测定依非韦伦片中有关物质的高效液相色谱-三重四极杆质谱联用(HPLC-TRIPLE QUAD-MS/MS)法,并推导质谱裂解途径。方法以十八烷基键合相硅胶为填料的色谱柱(4.6 mm×100 mm,3μm);流动相为0.1%甲酸(含2 mmol·L^(-1)甲酸铵)-甲醇(梯度洗脱);质谱采用电喷雾离子源(ESI),以正离子模式、多反应监测方式(MRM)进行定量分析。结果对依非韦伦和4种杂质的质谱图进行解析并推导其裂解途径。对检测方法进行了方法学验证,依非韦伦杂质A、杂质B和杂质C在1~500 ng·mL^(-1)内线性关系良好,杂质D在5~500 ng·mL^(-1)内线性关系良好;定量限在1.0~5.0 ng·mL^(-1);4种杂质的加样回收率在89.5%~95.3%。结论该方法专属性强、灵敏度高且准确度好,适用于依非韦伦片中有关物质的检查与控制。
Objective To establish an HPLC-TRIPLE QUAD-MS/MS method for determination of related substances in efavirenz tablets and to deduce their mass spectrometry fragmentation pathways.Methods The separation was carried out on a C18 column(4.6 mm×100 mm,3μm).The mobile phase was 0.1%formic acid(containing 2 mmol·L^(-1) ammonium formate)-methanol(gradient elution).An ion source ESI was used and quantification was in a positive ion mode in a multi-reaction monitoring mode(MRM).Results The mass spectra of efavirenz and four of its impurities were analyzed before the fragmentation pathways were deduced.The determination method was validified methodologically.Impurities A,B,and C had good linear relationships within the range of 1-500 ng·mL^(-1),while impurity D had a good linear relationship within the range of 5-500 ng·mL^(-1).The limits of quantification ranged from 1.0 to 5.0 ng·mL^(-1),while the average recovery ranged from 89.5%to 95.3%.Conclusion The established HPLC-TRIPLE QUAD-MS/MS method has a strong specificity,high sensitivity,and good accuracy.It is suitable for simultaneous quantitative determination of related substances in efavirenz tablets.
作者
刘毅
吴静芳
覃玲
陈俊苗
章娟
陈华
宁霄
曹进
LIU Yi;WU Jingfang;QIN Lin;CHEN Junmiao;ZHANG Juan;CHEN Hua;NING Xiao;CAO Jin(Institute for Chemical Drug Control,National Institutes for Food and Drug Control,Beijing 102629,China;Guangzhou Institute for Drug Control,Guangzhou Guangdong 510160,China;SCIEX China,Beijing 100015,China)
出处
《中国药物警戒》
2025年第7期749-754,共6页
Chinese Journal of Pharmacovigilance
基金
国家重点研发计划(2021YFC2401100)。
