HPLC-MS/MS法分析氟胞嘧啶中痕量基因毒性杂质N,N-二甲基苯胺

目的：建立液相色谱-质谱联用方法测定氟胞嘧啶中痕量基因毒性杂质N，N-二甲基苯胺的含量。方法：采用C₁₈（2.1 mm×100 mm，1.8 μm）色谱柱，以水（含0.1%甲酸）-甲醇（含0.1%甲酸）（95：5）为流动相，流速0.2 mL·min^-1，电喷雾离子化（ESI），正离子模式下MRM采集。结果：N，N-二甲基苯胺质量浓度在0.4~10 ng·mL^-1范围内，与峰面积线性关系良好（r=0.999 5）；检测限为0.1 ng·mL^-1，定量限为0.4ng·mL^-1；平均回收率（n=9）为101.3%。3批样品中N，N-二甲基苯胺的含量均小于0.02 μg·g^-1。结论：本方法可用于氟胞嘧啶中痕量基因毒性杂质N，N-二甲基苯胺含量的检测。

Objective: To establish an LC-MS/MS method for the determination of trace level of genotoxic impurity N, N-dimethylaniline in flucytosine.Methods: The C₁₈(2.1 mm×100 mm, 1.8 μm)analytical column was used for the separation with a mobile phase consisting of water-methanol-formic acid(95:5:0.1)at a flow rate of 0.2 mL·min^-1. The detection was achieved in ESI positive ion mode with MRM.Results: The calibration curve for N, N-dimethylaniline was in good linearity in the range from 0.4 to 10 ng·mL^-1(r=0.999 5). The limit of detection was 0.1 ng·mL^-1, and the limit of quantitation was 0.4 ng·mL^-1. Average recovery(n=9)was 101.3%. The contents of N, N-dimethylaniline in three batches of flucytosine were all lower than 000.02 μg·g^-1.Conclusion: The established method can be applied to the genotoxic impurity N, N-dimethylaniline determination in flucytosine.

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