HS-SPME-GC-MS as an alternative method for NDMA analysis in ranitidine products.

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.