Drug Reference Laboratory, Saudi Food & Drug Authority (SFDA), 12843-7116, Riyadh, Saudi Arabia.
Drug Reference Laboratory, Saudi Food & Drug Authority (SFDA), 12843-7116, Riyadh, Saudi Arabia.
J Pharm Biomed Anal. 2020 Nov 30;191:113582. doi: 10.1016/j.jpba.2020.113582. Epub 2020 Aug 21.
N-nitrosodimethylamine (NDMA) is a carcinogenic contaminant that was accidentally discovered in drugs, such as valsartan and ranitidine, and more recently in metformin. Liquid chromatography tandem mass spectrometry (LC-MS/MS) is the method typically used for the analysis of NDMA in ranitidine. It seems that using gas chromatography (GC) for NDMA analysis is problematic as ranitidine is sensitive to high temperatures. In the present study, we assessed the usefulness of solid-phase microextraction (SPME) as a method of extraction and introduction into the GC. When using headspace (HS) and liquid injection modes in GC for NDMA analysis in ranitidine, higher NDMA levels were detected compared to using LC-MS/MS. Interestingly, using HS-SPME-GC-MS was advantageous because we could avoid the high temperature utilized in the liquid injection and HS modes. Moreover, the results obtained using HS-SPME-GC-MS provided a good match with those achieved using LC-MS/MS. The feasibility of using HS-SPME-GC-MS to successfully analyze NDMA in ranitidine opens new opportunities for the analysis of this contaminant in pharmaceuticals, specifically those that are heat-labile.
N-亚硝基二甲胺（NDMA）是一种致癌污染物，它意外地在药物中被发现，如缬沙坦和雷尼替丁，最近又在二甲双胍中被发现。液相色谱串联质谱法（LC-MS/MS）通常用于分析雷尼替丁中的 NDMA。似乎使用气相色谱法（GC）分析 NDMA 存在问题，因为雷尼替丁对高温敏感。在本研究中，我们评估了固相微萃取（SPME）作为一种提取和引入 GC 的方法的有用性。当在 GC 中使用顶空（HS）和液体进样模式分析雷尼替丁中的 NDMA 时，与使用 LC-MS/MS 相比，检测到的 NDMA 水平更高。有趣的是，使用 HS-SPME-GC-MS 具有优势，因为我们可以避免液体进样和 HS 模式中使用的高温。此外，使用 HS-SPME-GC-MS 获得的结果与使用 LC-MS/MS 获得的结果非常吻合。HS-SPME-GC-MS 成功分析雷尼替丁中 NDMA 的可行性为分析热不稳定药物中的这种污染物开辟了新的机会。
