Piperazine / NPIP starting material

Piperazine, also known as 1,4-Piperazine, Antiren, Diethylenediamine, Dispermine, Hexahydropyrazine, Pipersol, Tetrahydro-1,4-diazine, and 1,4-Diazacyclohexane, is an important heterocyclic secondary diamine widely used as a starting material, intermediate, and building block in pharmaceutical and fine-chemical synthesis. It has the molecular formula C4H10N2, a molecular weight of 86.14 g/mol, and is associated with CAS No. 110-85-0. Due to its secondary amine functional groups, piperazine is susceptible to nitrosation in the presence of nitrites under acidic or nitrosating conditions, forming the potent nitrosamine impurity N-Nitrosopiperazine (NPIP).

While piperazine itself is not a nitrosamine, its ability to form NPIP places it under the strict oversight of global nitrosamine guidelines (USFDA, EMA, ICH M7). The resulting nitrosamine impurity N-Nitrosopiperazine (NPIP) is categorized under the USFDA CPCA Potency Category 1, with a stringent acceptable intake limit of 26.5 ng/day. Manufacturers using piperazine must therefore conduct comprehensive nitrosamine risk assessments, evaluate process conditions, identify nitrosation risk points, and implement controls to prevent NPIP formation or carryover. Piperazine is a key raw material employed in the synthesis of several active pharmaceutical ingredients (APIs), including antiparasitic agents, antihistamines, CNS drugs, and various piperazine-based intermediates. In pharmaceutical manufacturing, its primary relevance lies in its role as an NPIP precursor, requiring proactive strategies to prevent nitrosamine contamination through controlled processing, nitrite-free environments, and sensitive analytical testing (LC-MS/MS, GC-MS).

At Manasa Life Sciences, we support manufacturers working with piperazine by providing end-to-end nitrosamine risk assessment, precursor mapping, process evaluation, and development of ultra-sensitive analytical methods for detecting NPIP at trace levels. Our expertise ensures full regulatory compliance, strengthens impurity-control frameworks, and enhances drug safety and quality across development and commercial production.