Rapid Screening of Nitrosamine Impurities in Metformin Hydrochloride Tablets using Headspace Gas Chromatography Ion Mobility Spectrometry

The detection of potent carcinogenic nitrosamine impurities in pharmaceutical products has attracted significant regulatory attention in recent years, and advanced analytical methods are needed to accurately quantify nitrosamines in pharmaceutical products. In this study, a headspace gas chromatography-ion mobility spectrometry (HS-GC-IMS) method was proposed and validated, which addresses two key challenges: achieving the sub-ppb sensitivity required for low-concentration nitrosamine analysis, and reducing matrix interferences in extended-release formulations. Seven investigated nitrosamines showed good linearity (R 2 >0.99) in the range of 0.5-100 ng/mL, with limits of detection (LOD) of 0.05-0.51 ng/mL and limits of quantification (LOQ) of 0.16-1.70 ng/mL. Precision studies (intra-day relative standard deviation RSD<5%, inter-day RSD<13%) and satisfactory spiked recoveries (84.31%-106.60%) in active pharmaceutical ingredient matrices confirmed the robustness of this method. The developed method eliminates the need for complex extraction and pre-concentration procedures, requires minimal sample preparation and enables rapid gas chromatography separation.