LC-MS/MS测定艾司奥美拉唑钠中潜在基因毒性杂质2-氯甲基-3,5-二甲基-4-甲氧基吡啶

Determination of Potential Genotoxic Impurity 2-Chloromethyl-4-methoxy-3,5-dimethylpyridine in Esomeprazole Sodium by LC-MS/MS

目的:建立LC-MS/MS法测定艾司奥美拉唑钠中潜在基因毒性杂质2-氯甲基-3,5-二甲基-4-甲氧基吡啶。方法:色谱柱为Poroshell 120 EC-C18柱(50 mm×4.6 mm,2.7μm),柱温:30℃,流动相为水-乙腈(60∶40)(含0.2%甲酸),流速:0.5 ml·min^(-1)。采用电喷雾离子源(ESI),以多反应监测模式(MRM)进行正离子扫描,定量离子对为质荷比(m/z) 186→150.2,定性离子对为质荷比(m/z) 186→120.1。结果:在该色谱条件下,2-氯甲基-3,5-二甲基-4-甲氧基吡啶在0.825 8~165.166 7 ng·ml^(-1)浓度范围内线性关系良好(r=0.999 9),平均回收率为90.2%(RSD=1.6%,n=9),检测限为0.330 3 ng·ml^(-1),方法检测限为0.033μg·g^(-1)。结论:该分析方法简便高效,能有效准确的测定艾司奥美拉唑钠中的潜在基因毒性杂质2-氯甲基-3,5-二甲基-4-甲氧基吡啶。

Objective: To establish an HPLC-MS/MS analytical method for the determination of potential genotoxic impurity 2-chloromethyl-4-methoxy-3,5-dimethylpyridine in esomeprazole sodium. Methods: The separation was carried out on a Poroshell 120 EC-C18(50 mm×4.6 mm,2.7 μm) column at the column temperature at 30℃ and flow rate of 0.5 ml·min^(-1). The mobile phase was a mixture of 0.2% formic acid and 40% acetonitrile in water. Mass spectrometry was operated in electrospray ionization(ESI) with multiple reactions monitoring mode(MRM). The quantitative and qualitative ion pairs were m/z 186→150.2 and m/z 186→120.1. Results: The method had good specificity and promising linearity ranged from 0.825 8 ng·ml^(-1) to 165.166 7 ng·ml^(-1)(r = 0.999 9).The average recovery was 90.2%(RSD = 1.6%,n = 9). The detection limit and method detection limit was 0.330 3 ng·ml^(-1) and 0.033μg·g^(-1),respectively. Conclusion: The method is simple,accurate and reliable,which can be applied to determine 2-chloromethyl-4-methoxy-3,5-dimethylpyridine in esomeprazole sodium.