Isolation and Characterization of Related Impurity in Milnacipran Hydrochloride Active Pharmaceutical Ingredient.

Abstract

Milnacipran hydrochloride is an antidepressant drug, belonging to a class of selective serotonin re-uptake inhibitors. Unknown impurity in active pharmaceutical ingredient and pharmaceutical formulation of Milnacipran hydrochloride was found to be 0.08% and 0.12%, respectively, by peak area, with sensitive, isocratic RP-HPLC method. As per revised guidelines of International Conference on Harmonization Q3A (R2) and Q3B (R2), impurity profiling should be done for drug substances and drug products to identify and characterize all the unknown impurities that are present at level above 0.05%. This unknown impurity was targeted and isolated by developed Prep-HPLC method. The isolated impurity is characterized as 1-phenyl-3-azabicyclo [3.1.0] hexan-2-one using spectroscopic techniques like FT-IR, Mass, and NMR. The origin of the impurity is also postulated by proposing the plausible mechanism of formation.