ACCELERATED STABILITY STUDIES ON ENE-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 i n aqueous solutions, was investigated using reverse-phase high-perform ance 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 conditio ns. 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 i ncreasing storage temperature. The linearity of the Arrhenius plot ind icates that there is no change in the reaction mechanism within the te mperature range studied. In alkaline media, the drug degrades at a fas ter rate through hydrolytic rather than an oxidative mechanism. The ma jor hydrolytic degradation product, 16-methylene-17 alpha-hydroxy-19-n or-pregn-4-ene-3,20-dione, was separated and identified by mass spectr ometry.