Recently, N-nitrosamines have been unexpectedly found in generic sartan products. Herein, we developed a sensitive and stable GC-MS/MS method with multiple reactions monitoring mode for the simultaneous determination of four N-nitrosamines in sartan substances, namely, N-nitrosodimethylamine, N-nitrosodiethylamine, N-nitrosodibutylamine, and N-nitrosodiisopropylamine. The conditions of gas chromatography and mass spectrometry were optimized. The method was validated according to the International Council for Harmonization guidelines in terms of sensitivity, linearity, accuracy, precision, specificity, and stability. The limits of detection of N-nitrosamines in sartan substances ranged from 0.002 to 0.150 ppm, and the corresponding limits of quantification were in the range of 0.008-0.500 ppm, which met the sensitivity requirements for the limits set by the Food and Drug Administration of the United States. The internal standard curve of four N-nitrosamines showed good linearity of regression coefficients over 0.99. The recoveries of N-nitrosamines in selected sartan drugs ranged from 87.68 to 123.76%. The intraday and interday relative standard deviation values were less than 9.15%. Therefore, this proposed method exhibited good sensitivity and precision, high accuracy, and fast analysis speed, which provide a reliable method for quality control of N-nitrosamines in sartan products.

中文翻译：

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开发一种灵敏、稳定的 GC-MS/MS 方法，用于同时测定沙坦类物质中的四种 N-亚硝胺基因毒性杂质

最近，在通用沙坦类产品中意外发现了 N-亚硝胺。在此，我们开发了一种灵敏、稳定的多反应监测模式 GC-MS/MS 方法，用于同时测定沙坦类物质中的四种 N-亚硝胺，即 N-亚硝基二甲胺、N-亚硝基二乙胺、N-亚硝基二丁胺和 N-亚硝基二异丙胺. 对气相色谱和质谱条件进行了优化。该方法已根据国际协调委员会指南在灵敏度、线性、准确度、精密度、特异性和稳定性方面进行了验证。沙坦类物质中N-亚硝胺的检出限为0.002～0.150 ppm，相应的定量限为0.008～0.500 ppm，符合美国食品和药物管理局设定的限值的灵敏度要求。四种N-亚硝胺的内标曲线显示出良好的回归系数线性超过0.99。选定的沙坦类药物中 N-亚硝胺的回收率为 87.68% 至 123.76%。日内和日间相对标准偏差值均小于 9.15%。因此，该方法灵敏度和精密度好，准确度高，分析速度快，为沙坦类产品中亚硝胺的质量控制提供了可靠的方法。日内和日间相对标准偏差值均小于 9.15%。因此，该方法灵敏度和精密度好，准确度高，分析速度快，为沙坦类产品中亚硝胺的质量控制提供了可靠的方法。日内和日间相对标准偏差值均小于 9.15%。因此，该方法灵敏度和精密度好，准确度高，分析速度快，为沙坦类产品中亚硝胺的质量控制提供了可靠的方法。