富马酸喹硫平原料有关物质HPLC/LC-MS分析  

Analysis of Quetiapine Fumarate Related Substances by HPLC/LC-MS

作　　者：胡蝶[1] 杨满琴[1] 高玉菊 徐玥玮[1] 王丽[1] 高晓明[1] 盛竹君 张楠[1] Hu Die;Yang Manqin;Gao Yuju;Xu Yuewei;Wang Li;Gao Xiaoming;Sheng Zhujun;Zhang Nan(Department of Pharmacy,Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine,Hefei 230001,China)

机构地区：[1]安徽中医药大学第二附属医院药学部,合肥230001

出　　处：《中国药师》2022年第10期1814-1820,共7页China Pharmacist

基　　金：安徽省教育厅自然科学研究重点项目(编号:KJ2020A0792)。

摘　　要：目的:通过对潜在杂质分析,建立富马酸喹硫平原料有关物质检测方法,并利用液质联用(LC-MS)技术对降解杂质进行初步推导及结构鉴定。方法:采用Welch C_(18)(250 mm×4.6 mm,5μm)为色谱柱;以乙腈:1.6 g·L^(-1)醋酸铵的缓冲溶液(用氨水调节pH至7.0)(15∶85)为流动相A,乙腈为流动相B,梯度洗脱;检测波长为250 nm;柱温:45℃;流速:1.0 ml·min^(-1)。采用离子源(ESI)正离子模式采集数据,扫描范围:m/z100~2000;对富马酸喹硫平强制降解破坏样品进行测定,结合碎片的相对分子质量进行初步分析。结果:专属性试验表明可以有效分离并检出杂质,采用LC-MS推断出5个主要降解杂质化学结构及降解途径;杂质A、B、C、D、E、F、G、H、I、J的校正因子分别为0.98,0.92,0.55,1.02,0.86,1.04,0.82,0.97,0.93,0.82,回收率分别为99.5%,99.6%,99.2%,99.0%,97.4%,101.2%,98.9%,99.2%,98.8%,99.3%。结论:本方法专属性强、灵敏度高、准确度好,对富马酸喹硫平原料的杂质谱分析及质量控制具有重要意义。Objective:To establish a method for the detection of related substances in quetiapine fumarate raw material through the analysis of potential impurities,and to carry out preliminary derivation and structural identification of degradation impurities by liquid chromatography-mass spectrometry.Methods:A Welch C_(18)(250 mm×4.6 mm,5μm)column was used,and the buffer solution with acetonitrile∶1.6 g·L^(-1) ammonium acetate(pH was adjusted to 7.0 by ammonia)(15∶85)was the mobile phase A,acetonitrile was the mobile phase B,the detection wavelength was 250 nm,the column temperature was 45℃,and the flow rate was 1.0 ml·min^(-1).The data were collected in a positive ion mode of ion source(ESI),and the scanning range was m/z 100-2000;the forced degradation damage sample of quetiapine fumarate was determined,and the preliminary analysis was performed by combining relative molecular mass of the fragment.Results:The specificity test showed that the impurities could be effectively separated and detected,and the chemical structures and degradation pathways of the five main degraded impurities were deduced by LC-MS.The correcting factors of impurities A,B,C,D,E,F,G,H,I and J were 0.98,0.92,0.55,1.02,0.86,1.04,0.82,0.97,0.93 and 0.82,respectively.The recoveries were 99.5%,99.6%,99.2%,99.0%,97.4%,101.2%,98.9%,99.2%,98.8%and 99.3%,respectively.Conclusion:The method has strong specificity,high sensitivity and good accuracy,which is of great significance for the impurity spectrum analysis and quality control of quetiapine fumarate raw material.

关 键 词：富马酸喹硫平 有关物质 液质联用 

分 类 号：R927.11[医药卫生—药学]