摘要
目的:建立测定富马酸喹硫平片中有关物质的高效液相色谱方法(HPLC)并使用高分辨质谱法(HRMS)对各杂质峰归属进行验证。方法:采用Agilent 5 TC-C18(2)(250 mm×4.6 mm,5µm)色谱柱,以15mmol/L醋酸铵溶液和乙腈为流动相进行梯度洗脱,并考察了不同浓度、pH、柱温对分离效果的影响。质谱检测器采用HESI离子源,正离子检测模式,借助Mass Frontier 8.0和Compound Discoverer 3.3软件进行碎片和裂解分析,推测有关物质的结构,并采用标准品做对照,结合文献报道,验证推测结果的准确性。结果:在最佳条件下,各有关物质在该色谱条件下与主成分实现有效分离,喹硫平在0.01~1.5μg/mL浓度范围内线性关系良好(r=0.9999),检测限(LOD)为0.005μg/mL,定量限(LOQ)为0.016μg/mL。根据HRMS结果,共鉴定出富马酸喹硫平中的6种杂质。结论:该方法能够有效分离喹硫平及其多个杂质,具有简便、灵敏度高、专属性强、准确度高、耐用性强、可行性高的特点,可为富马酸喹硫平片有关物质的测定提供参考。
Objective:To establish a High-performance Liquid Chromatography(HPLC)method for the determination of related substances in quetiapine fumarate tablets.The impurities were identified by high resolution mass spectrometry(HRMS).Methods:Effects of different concentration,pH,column temperature on the separation for target compounds were compared.The target compounds were separated on an Agilent 5TC-C18(2)column(250 mm×4.6 mm,5µm)by gradient elution with 15 mmol/L ammonium acetate and acetonitrile as the mobile phases.The effects of different concentrations,pH,and column temperature on separation efficiency were investigated.The mass spectrometer was operated in HESI ion source,positive detection mode.Fragmentation analysis was used Mass Frontier 8.0 and Compound Discoverer 3.3 to verify and analyze the impurities.The structures of the impurities were speculated.Combined with the standards and the literature report,to verify the accuracy of the inferred results.Results:Under the optimized conditions,related substances were completely separated from the major constituents.Quetiapine showed good linear relationships within the range of 0.01~1.5μg/mL(r=0.9999),the limit of detection(LOD)was 0.005μg/mL,and the limit of quantification(LOQ)was 0.016μg/mL.According to the HRMS results,six impurities were speculated.Conclusion:This method can effectively separate quetiapine and its impurities,and has the characteristics of simple,high sensitivity,specificity,accuracy,durability and feasibility.It provides reference for the determination of related substances in Quetiapine fumarate tablets.
作者
黄诺哲
刘悉润
黄莹
Huang Nuozhe;Liu Xirun;Huang Ying(Guangdong Institute for Drug Control,NMPA Key Laboratory for Rapid Testing Technology of Drugs,Guangzhou 510663,China)
出处
《广东化工》
CAS
2024年第10期128-132,共5页
Guangdong Chemical Industry
基金
广东省药品检验所基金项目(ZA20200018)
广州市科技计划项目(202102080640)
广东省中医药局科研项目(20202023)。
