LC-MS/MS测定草酸右旋西酞普兰中对甲苯磺酸酯类基因毒性杂质的含量

Determination of Genotoxic Impurities in Escitalopram Oxalate by LC-MS/MS

关键词:  草酸右旋西酞普兰  对甲苯磺酸乙酯  对甲苯磺酸异丙酯  基因毒性  液质联用

Key words:  escitalopram oxalate  ethyl p-toluenesulfonate  isopropyl p-toluenesulfonate  genotoxic impurities  LC-MS

摘要:

目的 建立LC-MS/MS测定草酸右旋西酞普兰中对甲苯磺酸酯类基因毒性杂质的含量。方法 采用Zorbax Eclipse XDB C₁₈（250 mm×4.6 mm，5 μm）；流动相为20 mmol·L^-1乙酸铵水溶液-乙腈，梯度洗脱，流速为0.8 mL·min^-1；柱温为35℃；采用Ultimate 3000 HPLC-AB Science 4000 QTrap三重四极杆串联离子阱液质联用仪和多反应离子监测模式二级质谱MS/MS（ESI源）检测，正离子模式采集数据。结果 基因毒性杂质对甲苯磺酸乙酯和对甲苯磺酸异丙酯均在5~100 ng内与峰面积呈良好的线性关系，线性方程分别为y=1.19×10⁴x-140（r=0.999 5）和y=1.27×10³x-156（r=0.999 4），检测限分别为1 ng和2 ng，定量限分别为2 ng和4 ng，平均回收率分别为99.0%和101.0%；RSD分别为3.5%和4.7%（n=9）。结论 方法简便准确，可用于草酸右旋西酞普兰中对甲苯磺酸酯类基因毒性杂质的检测。

Abstract:

OBJECTIVE To establish an LC-MS/MS analytical method for the determination of genotoxic impurities in escitalopram oxalate. METHODS The method was achieved on a Zorbax Eclipse XDB C₁₈ column(250 mm×4.6 mm, 5 μm) utilizing a mobile phase of 20 mmol·L^-1 ammonium acetate(A)-acetonitrile(B) with gradient elution at the flow rate of 0.8 mL·min^-1. The temperature of column was set at 35℃. The Ultimate 3000 HPLC-AB Science 4000 QTrap Tripling Four bar LC-MS was used to detect ethyl p-toluenesulfonate and isopropyl p-toluenesulfonate(ESI source, in Multiple Reaction Monitoring positive mode). RESULTS Standard curve was linear in the range of 5-100 ng(r=0.999 9). The limit of quantification of ethyl p-toluenesulfonate and isopropyl p-toluenesulfonate were separately 1 ng and 2 ng. The limit of detection were 2 ng and 4 ng, respectively. The average recovery of ethyl p-toluenesulfonate and isopropyl p-toluenesulfonate were 99.0% and 101.0%, RSD were 3.5% and 4.7%(n=9). CONCLUSION The method is convenient and sensitive for the determination of genotoxic impurities in escitalopram oxalate.