高效液相色谱-四极杆/线性离子阱质谱法同时测定艾司奥美拉唑钠中2种潜在基因毒性杂质残留

Simultaneous Determination of Two Potential Genotoxic Impurities Residues in Esomeprazole Sodium by HPLC-QTRAP-MS/MS

建立了高效液相色谱-四极杆/线性离子阱质谱法(HPLC-QTRAP-MS/MS)同时测定艾司奥美拉唑钠中氮氧物(GTI E)和氮氧磺酰物(GTI I) 2种潜在基因毒性杂质痕量残留的分析方法。艾司奥美拉唑钠药物以30%(体积分数)乙腈水溶液溶解后,采用Agela VenusiL MP-C_(18)色谱柱(2.1 mm×100 mm,3μm)分离,以乙腈-水为流动相梯度洗脱,在流速0.2 mL/min,柱温35℃,进样量1μL,电喷雾负离子(ESI^-)扫描方式下以多反应离子监测(MRM)模式进行检测。结果表明,艾司奥美拉唑钠潜在基因毒性杂质GTI E和GTI I分别在1.26～44.8、1.34～45.2μg/L范围内线性关系良好,相关系数(r)分别为0.994 7和0.992 8,检出限(S/N=3)分别为0.381、0.384μg/L,定量下限分别为1.26、1.34μg/L,平均加标回收率分别为86.3%～87.6%和85.8%～91.4%,相对标准偏差(RSDs)分别为1.5%～2.2%和0.7%～4.0%。该方法操作简单、灵敏度高、重现性好,可用于艾司奥美拉唑钠药物中GTI E和GTI I 2种潜在基因毒性杂质的同时测定。

A high performance liquid chromatography-quadrupole ion trap mass spectrometric (HPLC-QTRAP-MS/MS )method was developed for the determination of two potential genotoxic impurities residues,i.e.omeprazole N-oxide (GTI E )and sulfonylate N-oxide (GTI I )in esomeprazole sodium.The esomeprazole sodium drugs were dissolved with 30 % acetonitrile-water (volume fraction ),and then separated on an Agela VenusiL MP-C 18 column (2.1 mm×100 mm,3 μm )by gradient elution using water-acetonitrile as mobile phases at a flow rate of 0.2 mL/min,a column temperature of 35 ℃ and an injection volume of 1 μL.The detection of analytes was performed in the negative electrospray ionization mode (ESI -)under multiple reaction monitoring (MRM )mode.As a result,the calibration curves for GTI E and GTI I showed good linearities in the ranges of 1.26-44.8 μg/L and 1.34-45.2 μg/L,with their correlation coefficients of 0.994 7 and 0.992 8,respectively.The limits of detection ( S/N =3 )and limits of quantitation ( S/N =10 )of the method were 0.381 and 0.384 μg/L,and 1.26 and 1.34 μg/L,respectively.The spiked recoveries for GTI E and GTI I were in the ranges of 86.3 %-87.6 % and 85.8 %-91.4 %,with the relative standard deviations (RSDs )of 1.5 %-2.2 % and 0.7 %-4.0 %,respectively.The method has the advantages of simple operation,high sensitivity,good reproducibility,and could be used for the simultaneous detection of two potential genotoxic impurities including GTI E and GTI I in esomeprazole sodium.