Identification and Structural Characterization of Secondary Degradant of Arformoterol Impurity in LDPE Respules of Arformoterol Tartrate Inhalation Solution

摘要

Arformoterol (R, R) is an enantiomer of racemic formoterol, was the first long-acting beta agonist (LABA), approved by U.S. food and Drug Administration (FDA). The Arformoterol which is used for the treatment of Chronic obstructive pulmonary disease (COPD) are inhaled bronchodilator drugs which are delivered directly to the patient’s airways through a different mechanism. The formulated drug product is kept for stability study as per ICH guideline [ 1 ] and during its stability interval analysis by HPLC (High performance liquid chromatography), an unknown peak observed at level around 0.1% which is well below the identification threshold of 0.5% but after heating it crossed the identification threshold. The approach to identify anonymous species of Arformoterol aqueous formulation was adopted as first to generate the impurity in sample, isolate, enrich and Characterize through LC-MS/MS and NMR Spectroscopy. Based on the spectral data the anonymous species was identified as an “Imine impurity”, it is secondary degradant of Amine impurity of Arformoterol formed due to reaction with leachable observed in LDPE respules.