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U.S. Department of Health and Human Services, Food and Drug Administration and Center for Drug Evaluation and Research (CDER) (2021) Control of Nitrosamine Impurities in Human Drugs, Guidance for Industry, Pharmaceutical Quality/Manufacturing Standards/Current Good Manufacturing Practice (CGMP) Revision 1.
https://www.fda.gov/media/141720/download

has been cited by the following article:

• TITLE: A Simple Liquid Chromatograph Method for Determination of Mass Spectrometric Method for Determination of Seven Nitrosamine Impurities in Cinacalcet Hydrochloride

  AUTHORS: Hanif Shaikh, Suresh Gaikwad, Mahesh Badane, Ashwini Mawal, Sanjay Jadhav, Parag Chavan

  KEYWORDS: Liquid Chromatography with mass Spectrometer (LC-MS), N-Nitrosodimethylamine (NDMA), N-Nitroso-N-Methyl-4-Aminobutyric Acid (NMBA), N-Nitrosodiethylamine (NDEA), N-Nitrosoethylisopropylamine (NEIPA), N-Nitrosodiisopropylamine (NDIPA), N-Nitrosomethylphenylamine (NMPA), N-Methyl-N-Nitrosopropane-1, 3-Diamine (Nitroso MAPA), LC-MS/MS, Cinacalcet Hydrochloride

  JOURNAL NAME: American Journal of Analytical Chemistry, Vol.16 No.9, September 17, 2025

  ABSTRACT: For the identification of the seven Nitrosamine Impurities i.e. N-Methyl-N-Nitrosopropane-1,3-diamine (Nitroso MAPA), N-Nitrosomethyl phenylamine (NMPA), N-Nitrosoethylisopropylamine (NEIPA), N-Nitroso-N-Methyl-4-Aminobutyric acid (NMBA), N-Nitrosodimethylamine (NDMA), N-Nitrosodiethylamine (NDEA), N-Nitrosodiisopropylamine (NDIPA) content in Cinacalcet Hydrochloride a sensitive, fast, linear, precise, and efficient liquid chromatography mass spectrometry method has been developed and validated. As a calcimimetics, cinacalcet hydrochloride is an active pharmaceutical ingredient that lowers blood calcium levels by telling the body to create less parathyroid hormone. It is known that amines react with nitrosating substances like nitrite to create nitrosamines. Residual amines in the APIs are the primary source of amines in the case of minor alkylnitrosamines like NDMA and NDEA. Although the degree of the risk of nitrosamine contamination has rarely been documented, residual amines in the APIs provide a possible problem. A simultaneous analytical method for amines that correspond to seven common small alkyl nitrosamines was developed and validated in this study. For every Nitrosamine Impurity, including N-Nitrosodimethylamine (NDMA), N-Nitroso-N-Methyl-4-Aminobutyric acid (NMBA), N-Nitrosodiethylamine (NDEA), N-Nitrosoethylisopropylamine (NEIPA), N-Nitrosodiisopropylamine (NDIPA), N-Nitrosomethylphenylamine (NMPA), and N-Methyl-N-Nitrosopropane-1,3-diamine (Nitroso MAPA), good linearity was obtained in the range of 0.009 ppm to 0.0450 ppm. The detection and quantification limits were 0.009 ppm. The range of recovery rates was 70% - 130%. With % RSD