Liu Jiao, Zhao Zhi, Yang Xiuling, Jin Yiran, Liu Xiujv, Wang Chuanping, Zhang Zhiqing
Department of Pharmacy, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China.
Iran J Pharm Res. 2021 Fall;20(4):255-264. doi: 10.22037/ijpr.2021.115222.15258.
A practical high-performance liquid chromatography-mass spectrometry method was developed for the analysis of -nitrosodimethylamine (NDMA) characterized as an impurity, in combination with reports of the carcinogen found in ranitidine samples. After simple extraction of ranitidine samples, all compounds were analyzed with a high-performance liquid chromatography-mass spectrometry. Sensitivity was enhanced by employing the ten-way valve switching technology, which was examined to allow NDMA to enter the mass spectrometry and cut out the ranitidine samples extremely. A good linear relationship was observed within 3-100 ng·mL (r = 0.9992). The validated approach was effectively used to evaluate the NDMA contents in ranitidine samples in circulation, which revealed a difference among 21 batches. Quantitative determination of NDMA was within the scope of 3.38-57.05 ng·mL. Moreover, the contamination levels of NDMA in seven batches of products from six manufacturers were listed to exceed the acceptable daily intake. The sensitive method was verified to be appropriate to determine NDMA, even with low contents of NDMA in ranitidine products; the analysis of the selected samples reveals that some samples exceeded the national limit requirements. Therefore, it is worthwhile to conduct comprehensive quality control of the other drugs containing NDMA.
建立了一种实用的高效液相色谱 - 质谱法，用于分析作为杂质的N - 亚硝基二甲胺（NDMA），结合雷尼替丁样品中发现的这种致癌物的报告。雷尼替丁样品经简单萃取后，所有化合物均采用高效液相色谱 - 质谱法进行分析。通过采用十通阀切换技术提高了灵敏度，该技术经检测可使NDMA进入质谱并极有效地排除雷尼替丁样品。在3 - 100 ng·mL范围内观察到良好的线性关系（r = 0.9992）。该验证方法有效地用于评估流通中雷尼替丁样品中的NDMA含量，结果显示21个批次之间存在差异。NDMA的定量测定范围为3.38 - 57.05 ng·mL。此外，列出了来自六个制造商的七批次产品中NDMA的污染水平超过了每日可接受摄入量。验证了该灵敏方法适用于测定雷尼替丁产品中含量较低的NDMA；对所选样品的分析表明，一些样品超出了国家限量要求。因此，对其他含NDMA的药物进行全面质量控制是值得的。
