The Identification of Naloxone-Related Drug Product Degradants

This study describes the identification of 15 degradants of naloxone produced in a buprenorphine/naloxone combination drug product. Accurate mass spectrometry was used to assign a chemical formula to each of the 15 degradants. The identities of five degradants were confirmed by comparison to authentic samples. The structural elucidation for six degradants was determined following NMR analysis of forced degradation samples. The identity of the remaining four degradants was inferred from mass spectrometry data. All degradants were a result of oxidation; six degradants had incorporated one molecule of oxygen, three degradants had incorporated two molecules of oxygen, one degradant had incorporated three molecules of oxygen, one degradant had incorporated one molecule of oxygen but had lost two molecules of hydrogen, two degradants had incorporated one molecule of oxygen and two molecules of hydrogen, one degradant was isomeric with naloxone, and the final degradant had incorporated one molecule of oxygen but had lost one molecule of carbon.