title: Isolation and structure elucidation of the major photodegradation products of loteprednol etabonate.
abstract: Photodegradation of loteprednol etabonate (5), a steroid anti-inflammatory drug, in the solid state, in aqueous suspension, and in aqueous acetonitrile solution has been investigated. Analysis by HPLC showed that the profile of photodegradation products in the solid state was qualitatively similar to that in the aqueous suspension, although the profile in the aqueous acetonitrile solution was considerably different. The major photodegradation products were isolated from the aqueous suspension and the aqueous acetonitrile solution by using preparative reversed-phase HPLC and their structures were elucidated on the basis of spectroscopic data. Photolysis in the solid state and in aqueous suspension yielded three rearrangement products, chloromethyl 17alpha-ethoxycarbonyloxy-11beta-hydroxy-5alpha-methyl-2-oxo-19-norandrosta-1(10),3-diene-17beta-carboxylate (8), chloromethyl 17alpha-ethoxycarbonyloxy-11beta-hydroxy-1-methyl-3-oxo-6(5-->10alpha)-abeo-19-norandrosta-1,4-diene-17beta-carboxylate (9), and chloromethyl 1beta,11beta-epoxy-17alpha-ethoxycarbonyloxy-2-oxo-10alpha-androsta-4-ene-17beta-carboxylate (10). In aqueous acetonitrile solution, 10 was the major product, however, 8 and 9 were not obtained. Pathways for the formation of these compounds from loteprednol etabonate (5) are proposed.
authors.affiliation: Senju Pharmaceutical Co, Ltd, 1-5-4, Murotani Nishi-ku, Kobe, Hyogo 651-2241, Japan. shirasaki@senju.co.jp
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Shirasaki
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Inada
authors.forename: Jun
authors.initials: J
authors.lastname: Inoue
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nakamura
mesh_terms: D000730:Androstadienes / Q000737:chemistry / Q000528:radiation effects*; D002851:Chromatography, High Pressure Liquid; D000069559:Loteprednol Etabonate; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010782:Photolysis; D014466:Ultraviolet Rays
chemical_list: D000730:Androstadienes; D000069559:Loteprednol Etabonate