HPLC-MS/MS法测定盐酸曲唑酮原料药中相关杂质的研究  

Determination of related impurities in trazodone hydrochloride API by HPLC-MS/MS

作　　者：奉艳花 邓鸣 FENG Yanhua;DENG Ming(Guangxi Institute for Drug Control,Nanning 530021,China)

机构地区：[1]广西壮族自治区药品检验研究院,南宁530021

出　　处：《中国药品标准》2024年第4期372-375,共4页Drug Standards of China

基　　金：广西壮族自治区药品监督管理局药品安全科研项目(桂药监科直属[2023]047号);广西壮族自治区药品监督管理局科研计划项目(桂药监直属2022-08)。

摘　　要：目的:建立高效液相色谱-串联质谱(HPLC-MS/MS)法测定盐酸曲唑酮中相关杂质的含量。方法:采用Agilent ZORBAX Eclipse Plus C_(18)色谱柱(2.1 mm×100 mm, 1.8μm),以0.1%甲酸溶液-乙腈为流动相,梯度洗脱,流速0.2 mL·min^(-1),柱温30℃,采用电喷雾离子化源(ESI),多反应检测(MRM)模式,正离子模式扫描。结果:测定了盐酸曲唑酮原料药中的5个相关杂质,分别为三唑并吡啶酮、曲唑酮-N-氧化物、脱氯曲唑酮、4-乙基曲唑酮、曲唑酮异丁醚类似物,杂质在测定的质量浓度范围内线性关系良好,r均≥0.999 5;平均回收率为91.9%~99.4%,RSD≤3.9%;测定的3批原料药中均检出了曲唑酮N-氧化物和脱氯曲唑酮,其中2批还检测到极微量的4-乙基曲唑酮。结论:建立的方法可测定盐酸曲唑酮原料药中的5种相关杂质,能更有效的评估和控制其质量。Objective:To establish an HPLC-MS/MS method for the determination of related impurities in trazodone hydrochloride API.Methods:The impurities were separated on an Agilent ZORBAX Eclipse Plus C 18 column(2.1 mm×100 mm,1.8μm)using a gradient elution of 0.1%formic acid solution and acetonitrile at a flow rate of 0.2 mL·min^(-1) at column temperature of 30℃,and determined by electrospray ionization source(ESI)combined with multiple reaction detection(MRM)in the positive ion mode.Results:The related impurities(triazolopyridone,trazodone N-oxide,dechlorinated trazodone,4-ethyltrazodone,and trazodone isobutyl ether analogue)in trazodone hydrochloride API were determined.The linear relationship of five impurities was good in corresponding concentration ranges with correlation coefficients(r)of more than 0.9995.The average recoveries varied between 91.9%and 99.4%with RSD≤3.9%.Trazodone N-oxide and dechlorinated trazodone were detected in all three batches,and extremely trace amounts of 4-ethyltrazodone were detected in two batches.Conclusion:The established method can determine the content of five related impurities in trazodone hydrochloride API,and can more effectively evaluate and control the quality of trazodone hydrochloride API.

关 键 词：高效液相色谱-串联质谱法 盐酸曲唑酮 相关杂质 含量测定 

分 类 号：R921.2[医药卫生—药学]