ACCELERATED STABILITY STUDIES ON 16-METHYLENE-17-ALPHA-ACETOXY-19-NOR-PREGN-4-ENE-3,20-DIONE (NESTORONE(TM))

The stability of the contraceptive steroid, Nestorone (16-methylene-17 alpha-acetoxy-19-nor-pregn-4-ene-3,20-dione) in the solid state and in aqueous solutions, was investigated using reverse-phase high-performance liquid chromatography. In the solid state, whether as a powder or when it is incorporated into Silastic implants, the steroid does nor undergo detectable degradation even under severe experimental conditions. In solution, the drug undergoes slow degradation that is dependent on temperature and pH of the medium. The decomposition is defined by first-order mechanism. As expected, the reaction rate increases with increasing storage temperature. The linearity of the Arrhenius plot indicates that there is no change in the reaction mechanism within the temperature range studied. In alkaline media, the drug degrades at a faster rate through hydrolytic rather than an oxidative mechanism. The major hydrolytic degradation product, 16-methylene-17 alpha-hydroxy-19-nor-pregn-4-ene-3,20-dione, was separated and identified by mass spectrometry.