Studies on Betamethasone : Behavior of Betamethasone in Acid or Alkaline Medium, Photolysis, and Oxidation

Abstract

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.