Diphenylamine/ NDPhA Starting material

Diphenylamine, also known as N-Phenylbenzenamine, Anilinobenzene, (Phenylamino)benzene, N,N-Diphenylamine, and N-Phenylaniline, is an important aromatic secondary amine widely used as a starting material, stabilizer, and chemical intermediate in pharmaceutical synthesis and various industrial applications. It has the molecular formula C12H11N, a molecular weight of 169.23 g/mol, and is associated with CAS No. 122-39-4. Although Diphenylamine itself is not a nitrosamine, its secondary amine structure enables it to undergo nitrosation under specific conditions involving nitrite sources and acidic or nitrosating environments, potentially leading to the formation of the nitrosamine impurity N-Nitrosodiphenylamine (NDPhA).

N-Nitrosodiphenylamine (NDPhA) is classified as a carcinogenic nitrosamine, and under the USFDA Carcinogenic Potency Categorization Approach (CPCA) it is assigned to Potency Category 3, with an acceptable intake limit of 96 ng/day. Therefore, when Diphenylamine is used as a starting material or intermediate, manufacturers must assess the risk of NDPhA formation, evaluate nitrosation-prone steps, and implement sensitive analytical controls (LC-MS/MS, GC-MS) to ensure NDPhA is not introduced into APIs or finished drug products. Compliance with USFDA, EMA, and ICH M7 guidelines requires strong control strategies and documented nitrosamine prevention practices. Diphenylamine is used in the production of pharmaceutical intermediates, antioxidants, dyes, agrochemicals and polymer stabilizers. In pharmaceutical manufacturing, its relevance primarily lies in its role as a nitrosamine precursor, requiring proactive monitoring and mitigation to maintain product quality and regulatory compliance.

At Manasa Life Sciences, we assist manufacturers using Diphenylamine by providing comprehensive nitrosamine risk assessments, precursor mapping, process optimization, and development of high-sensitivity analytical methods specifically designed to detect NDPhA at trace levels. Our expertise ensures strong impurity-control practices, full regulatory alignment, and enhanced product and patient safety throughout development and commercial manufacturing.