目的:建立超高效液相色谱离子阱高分辨质谱联用（UPLC-MS/MS）法测定乙酰唑胺及其制剂中遗传毒性杂质双硫脲的含量。方法:采用NanoChrom ChromCoreTM120 C18（2.1 mm×150 mm, 5 μm）色谱柱, 流动相为10 mmol·L-1 甲酸铵溶液- 甲醇（95∶5）, 流速0.2 mL·min-1, 柱温为30 ℃, 检测方式为正离子（ESI+）模式下平行反应监测（PRM）。结果:双硫脲杂质在0.048 3~0.181 0 μg·mL-1 范围内线性关系良好（r=0.999 2）, 原料的平均回收率为95.9%, 制剂的平均回收率为98.5%, 9 批次样品均未检出双硫脲。结论:该方法准确, 专属性强, 灵敏度高, 可用于乙酰唑胺及其制剂中双硫脲的痕量分析, 也为其他药物中双硫脲的测定提供参考。
Objective：To establish an UPLC-MS/MS method for the determination of genotoxic impurity dithiourea in acetazolamide and its preparations. Methods：The analytes were separated on a NanoChrom ChromCoreTM120 C18 column (2.1 mm×150 mm, 5 μm) maintained at 30 ℃, with the mobile phase of 10 mmol·L-1 ammonium formate solutionmethanol (95∶5) at a flow rate of 0.2 mL·min-1.The target compound was analyzed by the positive ion parallel reaction monitoring (PRM) mode. Results：The linear range of dithiobiurea was in the range of 0.048 3-0.181 0 μg·mL-1 (r=0.999 2), the average recoveries of raw material and prapation were 95.9% and 98.5%, respectively. No dithiobiurea was detected in 9 batches of samples. Conclusion：This method is accurate, specific and sensitive. It can be used for trace analysis of dithiobiurea in acetazolamide and its preparations, and can also provide reference for the deternination of dithiobiurea in other drugs.
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