The Identification\nof Naloxone-Related Drug Product\nDegradants

This study describes the identification of 15 degradants\nof naloxone\nproduced in a buprenorphine/naloxone combination drug product. Accurate\nmass spectrometry was used to assign a chemical formula to each of\nthe 15 degradants. The identities of five degradants were confirmed\nby comparison to authentic samples. The structural elucidation for\nsix degradants was determined following NMR analysis of forced degradation\nsamples. The identity of the remaining four degradants was inferred\nfrom mass spectrometry data. All degradants were a result of oxidation;\nsix degradants had incorporated one molecule of oxygen, three degradants\nhad incorporated two molecules of oxygen, one degradant had incorporated\nthree molecules of oxygen, one degradant had incorporated one molecule\nof oxygen but had lost two molecules of hydrogen, two degradants had\nincorporated one molecule of oxygen and two molecules of hydrogen,\none degradant was isomeric with naloxone, and the final degradant\nhad incorporated one molecule of oxygen but had lost one molecule\nof carbon.