UPLC-MS/MS法测定利伐沙班中的基因毒性杂质  

Determination of genotoxic impurity in rivaroxaban by UPLC-MS/MS

作　　者：侯继鹏 时晓燕 张业华 郝贵周 张贵民 HOU Ji-peng;SHI Xiao-yan;ZHANG Ye-hua;HAO Gui-zhou;ZHANG Gui-min(Lunan Pharmaceutical Group,National Engineering Research Center of Chiral Drugs,Linyi Shandong 273400)

机构地区：[1]鲁南制药集团股份有限公司,国家手性制药工程技术研究中心,山东临沂273400

出　　处：《中南药学》2023年第5期1363-1366,共4页Central South Pharmacy

摘　　要：目的建立超高效液相色谱-串联质谱法(UPLC-MS/MS)测定利伐沙班中基因毒性杂质(S)-2-(2-羟基-氯丙基)-1H-异吲哚-1,3-二酮。方法采用Thermo Hypersil Gold C18(2.1 mm×100 mm,3μm)色谱柱;流动相为0.1%甲酸(A)-0.1%甲酸乙腈(B),梯度洗脱;流速0.2 mL·min^(-1),柱温25℃;质谱采用电喷雾离子(ESI)源正离子扫描、多反应监测(MRM)模式对(S)-2-(2-羟基-氯丙基)-1H-异吲哚-1,3-二酮同时进行定性、定量检测。结果(S)-2-(2-羟基-氯丙基)-1H-异吲哚-1,3-二酮在1.50~29.96 ng·mL-1与峰面积线性关系良好(r=0.9991);平均回收率在99.72%~101.51%,RSD均小于5%;检测限和定量限分别为0.45 ng·mL^(-1)和1.50 ng·mL^(-1),6批利伐沙班样品中均未检出杂质。结论该方法灵敏度高,专属性强,可用于测定利伐沙班中基因毒性杂质(S)-2-(2-羟基-氯丙基)-1H-异吲哚-1,3-二酮。Objective To determine the genotoxic impurities(S)-2-(2-hydroxyl-chloropropyl)-1Hisoindole-1,3-diketone in rivaroxaban by ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS).Methods A Thermo Hypersil Gold C18 column(2.1 mm×100 mm,3μm)was used,with the mobile phase of 0.1%formic acid(A)and 0.1%formic acid acetonitrile(B)by gradient elution at a flow rate of 0.2 mL·min^(-1).The column temperature was 25℃.Multiple reaction monitoring was performed on a mass spectrometer equipped with an electrospray ion source in the positive mode to qualitatively and quantitatively detect(S)-2-(2-hydroxyl-chloropropyl)-1Hisoindole-1,3-diketone,simultaneously.Results The linearity for(S)-2-(2-hydroxyl-chloropropyl)-1H-isoindole-1,3-diketone was 1.50~29.96 ng·mL^(-1)(r=0.9991).The average recovery was 99.72%~101.51%,with RSD<5%.The LOD and LOQ were 0.45 ng·mL^(-1)and 1.50 ng·mL^(-1),respectively.No impurities were detected in 6 batches samples.Conclusion The method is sensitive and specific in the quantification of genotoxic impurities of(S)-2-(2-hydroxyl-chloropropyl)-1Hisoindole-1,3-diketone in rivaroxaban.

关 键 词：利伐沙班 基因毒性杂质 (S)-2-(2-羟基-氯丙基)-1H-异吲哚-1 3-二酮 超高效液相色谱-串联质谱 

分 类 号：R927[医药卫生—药学]