N-Nitrosodiethanolamine

N-Nitrosodiethanolamine (NDELA) also known as Nitrosobis(2-hydroxyethyl)amine, 2,2’-(Nitrosoimino)bisethanol, Diethanolnitrosamine, N,N-Diethanolnitrosamine, and N,N-bis(2-hydroxyethyl)nitrous amide is a nitrosamine impurity of significant toxicological and regulatory concern. NDELA has the molecular formula C₄H₁₀N₂O₃, a molecular weight of 134.13 g/mol, and is commonly associated with CAS No. 1116-54-7. Although not intentionally used in manufacturing, it may form unintentionally through nitrosation of Diethanolamine (DEA) or related amino alcohols in the presence of nitrite sources or acidic nitrosating conditions. Under the current U.S. FDA nitrosamine bases, NDELA does not have a compound-specific acceptable intake limit published; therefore, it is evaluated under the FDA’s Carcinogenic Potency Categorization Approach (CPCA). Based on structural characteristics, NDELA falls within Potency Category 5, which corresponds to the FDA default acceptable intake limit of 1,500 ng/day. This categorization aligns with the conservative approach used by global regulatory bodies including the FDA, EMA, and ICH M7, all of which require strong assessment and control of nitrosamine impurities such as NDELA in APIs, excipients, and finished drug products.

At Manasa Life Sciences, we assist pharmaceutical and chemical manufacturers in evaluating and controlling the risk of NDELA formation through comprehensive nitrosamine risk assessments, detailed route-of-synthesis evaluation, and development and validation of high-sensitivity analytical methods (LC-MS/MS, GC-MS) capable of detecting NDELA at trace levels. Our expertise ensures full compliance with global nitrosamine guidelines, supports strong impurity-control strategies, and enhances product quality and patient safety throughout the entire manufacturing lifecycle.