N-Nitroso N-Desmethyl Pheniramine

N-Nitroso N-Desmethyl Pheniramine is a genotoxic and potentially carcinogenic nitrosamine impurity associated with pheniramine, a first-generation H₁-antihistamine widely used for the symptomatic treatment of allergic rhinitis, urticaria, and other allergic conditions. Pheniramine is commonly available in oral dosage forms (tablets, syrups) and injectable formulations, often in combination products. Chemically, this impurity is described as N-methyl-N-(3-phenyl-3-(pyridin-2-yl)propyl)nitrous amide, which originates from nitrosation of the secondary amine present in the N-desmethyl pheniramine moiety. Cas.no: N/A ; Molecular formula: C15H17N3O ; Molecular weight: 255.31 g/mol.

The formation of N-Nitroso N-Desmethyl Pheniramine may occur during API synthesis, downstream processing, or degradation, particularly when nitrite sources or nitrosating agents are present under acidic, oxidative, or high-humidity conditions that favor nitrosation reactions. Structurally, it is a complex, it is classified under the USFDA Carcinogenic Potency Categorization Approach (CPCA) as Potency Category 1, with acceptable intake limit of 26.5 ng/day, in line with USFDA, EMA, and ICH M7 (R1) guidelines for the control of genotoxic impurities.

At Manasa Life Sciences, we assist pharmaceutical manufacturers in the effective management of N-Nitroso N-Desmethyl Pheniramine by conducting comprehensive nitrosamine risk assessments, identifying nitrosation-prone synthetic steps and degradation pathways, and evaluating potential contributions from raw materials, reagents, solvents, and excipients. We also develop and validate high-sensitivity analytical methods, including LC-MS/MS and GC-MS, for reliable trace-level detection and quantification. Our integrated scientific and regulatory approach strengthens nitrosamine control strategies, ensures GMP and global regulatory compliance, and helps safeguard product quality and patient safety throughout drug development and commercial manufacturing.