In order to investigate the stability of betamethasone (I) in the pharmaceutical preparation, degradation in acid or alkaline medium, photolysis, and oxidation reaction of I were performed under various conditions. On degradation in acid medium, I gave a mixture of two isomers of 9α-fluoro-11β, 20-dihydroxy-16β-methylpregna-1, 4, 17 (20)-trien-21-al-3-one, (IIa) and (IIb), and 9α-fluoro-11β, 21-dihydroxy-16-methylpregna-1, 4, 16-triene-3, 20-dione (III). On the other hand, in alkaline conditions, I afforded two products, 9α-fluoro-11β, 17α-dihydroxy-16β-methylandrosta-1, 4-dien-3-one-17-carboxylic acid (IV) and 9α-fluoro-11β-hydroxy-16β-methylandrosta-1, 4-diene-3, 17-dione (V). Compound V was also obtained by oxidation with KMnO4. The photolysis product, 9α-fluoro-11β, 17α, 21-trihydroxy-16β-methyl-1, 5β-cyclopregn-3-ene-2, 20-dione (VI) was obtained by photo rearrangement of the 1, 4-diene-3-keto steroid in considerable yield.
