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@article{187892,
        author = {Mr. Jigneshkumar Naginbhai Patel and Dr. Archana Deokar},
        title = {Development of an Analytical Method for Quantifying Nitrosamine Impurities in Metformin Using Liquid Chromatography-Mass Spectrometry},
        journal = {International Journal of Innovative Research in Technology},
        year = {2025},
        volume = {12},
        number = {7},
        pages = {33-42},
        issn = {2349-6002},
        url = {https://ijirt.org/article?manuscript=187892},
        abstract = {Nitrosamine-containing active pharmaceutical ingredients (APIs) have raised safety concerns due to their potential carcinogenic nature. Regulatory agencies such as the United States Food and Drug Administration (FDA) have established guidelines limiting nitrosamine impurities, including N-Nitrosodimethylamine (NDMA) and N-Nitrosodiethylamine (NDEA), among others. To ensure compliance, this study presents an analytical method for detecting and quantifying nitrosamine impurities in Metformin hydrochloride API, utilizing liquid chromatography coupled with mass spectrometry (LC-MS/MS). A Waters XSelect High Strength Silica (HSS) pentafluoro phenyl (PFP) column was employed for chromatographic separation, using a mobile phase gradient composed of 0.1% methanoic acid in water and methanol. Under the optimized analytical conditions, the retention times for Metformin hydrochloride, NDMA, NDEA, NEIPA, NMPA, and NDBA were 8.47, 15.83, 19.35, 20.54, 22.11, and 24.85 minutes, respectively, demonstrating efficient separation with good resolution for all analytes.The linearity assessment showed that NDMA exhibited a linearity range of 0.019–0.135 ppm, while NDEA, NEIPA, NMPA, and NDBA each showed linearity within the range of 0.002–0.10 ppm. The correlation coefficients (r) were 0.9913 for NDMA, 0.9973 for NDEA, and 0.9967 for NEIPA, NMPA, and NDBA, confirming excellent linearity, with corresponding regression coefficients (R²) of 0.9828, 0.9967, and 0.9934, respectively. The method demonstrated strong sensitivity, with LOD values of 0.0012 ppm (NDMA), 0.0056 ppm (NDEA), 0.0052 ppm (NEIPA), 0.0042 ppm (NMPA), and 0.0044 ppm (NDBA), and LOQ values of 0.0124, 0.0091, 0.0083, 0.0057, and 0.0067 ppm, respectively. Accuracy and recovery results were within the acceptable ICH limits, confirming the reliability of the method for quantitative analysis. Robustness evaluation, performed by varying critical parameters by ±10%, demonstrated consistent performance in accordance with ICH validation criteria. Furthermore, the developed method aligns with FDA guidelines for LOD and LOQ, ensuring suitability for routine analysis of nitrosamine impurities in pharmaceutical products. The approach also optimizes solvent consumption while maintaining essential sensitivity and specificity for detecting nitrosamine impurities in Metformin hydrochloride. Overall, the method meets ICH requirements, demonstrating high efficiency, sensitivity, good resolution, and reliability for regulatory and quality-control applications.},
        keywords = {Nitrosamine, Carcinogenic, Metformin hydrochloride, X select HSS PFP, LC-MS/MS},
        month = {November},
        }