UPLC-MS/MS法测定厄贝沙坦原料药中 8种亚硝胺杂质

摘要/Abstract

摘要： 目的：建立同时测定厄贝沙坦原料药中8种亚硝胺化合物的超高效液相色谱-串联质谱（UPLC-MS/MS）方法。方法：采用Waters XBridge C18色谱柱（4.6 mm×150 mm， 5 μm），以0.1%甲酸水（A）-甲醇（B）为流动相，梯度洗脱，流速1.0 mL·min-1，柱温40 ℃，进样体积40 μL；质谱离子源为APCI，正离子模式，多反应监测（MRM）采集。结果：该方法的检测限和定量限范围分别在0.07～1.02 ng·mL-1和0.25～3.41 ng·mL-1之间。8种亚硝胺化合物浓度在0.25～23.87 ng·mL-1范围内，线性关系良好，r2>0.99；回收率（n=9）平均值为85.9%～104.9%，RSD值为14.19%～21.01%；重复性RSD值为3.51%～11.09%，中间精密度RSD值为8.52%～19.96%。结论：本方法专属性强、灵敏度高，可用于测定厄贝沙坦原料药中8种亚硝胺杂质的含量，为其原料药质量控制提供数据支持。

关键词: font-size:medium, ">基因毒性杂质；N-亚硝胺类化合物；厄贝沙坦；超高效液相色谱-串联质谱

Abstract: Objective：To establish a specific method for simultaneous determination of eight N-nitrosamine impurities in irbesartan using UPLC-MS/MS technique. Methods：The separation was performed on a Waters XBridge C18 column(4.6mm×150mm，5μm) with the mobile phase consisting of 0.1% formic acid aqueous solution(mobile phase A) and methanol(mobile phase B) by gradient elution at the rate of 1.0 mL·min-1. The column temperature was 40℃. Multiple reaction monitoring(MRM) was performed on a triple quadrupole mass spectrometer equipped with APCI source in positive mode for the quantitative detection of eight N-nitrosamine impurities with injection volume of 40 μL. Results： The limit of detection(LOD) and limit of quantification(LOQ) were between 0.07-1.02 ng·mL-1 and 0.25-3.41 ng·mL-1 respectively. The calibration curve was linear(r2＞0.99) over the concentration range of 0.25-23.87 ng·mL-1 for eight compounds. The method also afforded satisfactory results in terms of recoveries(n=9， 85.9%-104.9%，RSD14.19%-21.01%)，intra-and inter-day precisions(3.51%-11.09% and 8.52%-19.96% separately). Conclusion： The developed method has been employed to determinate eight N-nitrosamine impurities and control the quality of irbesartan due to its sensitivity and accuracy.

Key words: font-size:medium, ">Genotoxic impurities；N-nitrosamines；Irbesartan；Ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)

中图分类号:

彭燕, 杨云帆, 赵兰玲, 杜金蔚, 林妮妮, 董颖. UPLC-MS/MS法测定厄贝沙坦原料药中 8种亚硝胺杂质[J]. 中国药物评价, 2022, 39(3): 199-203.

PENG Yan, YANG Yun-fan, ZHAO Lan-ling, DU Jin-wei, LIN Ni-ni, DONG Ying. Determination of Eight N-nitrosamine Impurities in Irbesartan by UPLC-MS/MS[J]. CHINESE JOURNAL OF DRUG EVALUATION, 2022, 39(3): 199-203.

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