Morpholine / NMOR Starting material

Morpholine, also known as Tetrahydro-1,4-oxazine, is a versatile heterocyclic secondary amine widely used as a starting material, solvent, reagent, and intermediate in pharmaceutical and chemical synthesis. It has the molecular formula C4H9NO, a molecular weight of 87.12 g/mol, and is associated with CAS No. 110-91-8. Due to its secondary amine structure, morpholine has the potential to undergo nitrosation in the presence of nitrite sources under acidic or nitrosating conditions, forming the nitrosamine impurity N-Nitrosomorpholine (NMOR) a compound of significant toxicological concern.

While Morpholine itself is not a nitrosam ine, its nitrosated derivative N-Nitrosomorpholine (NMOR) is classified by the USFDA Carcinogenic Potency Categorization Approach (CPCA) as a Potency Category 1 nitrosamine, with a strict acceptable intake limit of 26.5 ng/day. Regulatory bases including USFDA, EMA, and ICH M7 require manufacturers to evaluate the potential for NMOR formation, assess nitrosation-prone steps, prevent introduction of nitrite contaminants, and implement high-sensitivity analytical methods (LC-MS/MS, GC-MS) to ensure control at trace levels. Morpholine is commonly used in the production of APIs, intermediates, corrosion inhibitors and surfactants. In pharmaceutical manufacturing, its relevance lies in its function as a nitrosamine precursor, requiring stringent control of pH, raw-material quality, environmental conditions, and nitrite contamination to ensure safe and compliant API production.

At Manasa Life Sciences, we support manufacturers using Morpholine through comprehensive nitrosamine risk assessments, precursor mapping, process optimization, and development/validation of ultra-sensitive analytical methods specifically targeting NMOR. Our expertise ensures strong impurity-control strategies, global regulatory compliance, and enhanced product quality and patient safety throughout the drug development and manufacturing lifecycle.