TY - JOUR T1 - Degradation Products of Beclomethasone Dipropionate in Human Plasma JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 132 LP - 137 VL - 26 IS - 2 AU - Kuncoro Foe AU - H.T. Andrew Cheung AU - Bruce N. Tattam AU - Kenneth F. Brown AU - J. Paul Seale Y1 - 1998/02/01 UR - http://dmd.aspetjournals.org/content/26/2/132.abstract N2 - The anti-inflammatory glucocorticosteroid beclomethasone dipropionate was found previously to degrade in human plasma at 37°C to yield beclomethasone 17-monopropionate, beclomethasone 21-monopropionate, and beclomethasone together with three unknown species, D-1, D-2, and D-3. In this paper, we report the isolation of D-2 and D-3 by preparative HPLC and the elucidation of their structures. Both products D-2 and D-3 exhibited UV bathochromic shifts relative to beclomethasone dipropionate of 9 nm. From the mass spectrometry and 1H-NMR data, it is concluded that D-2 and D-3 are formed from beclomethasone and beclomethasone 21-monopropionate, respectively, with the loss of hydrogen chloride and the formation of a 9,11-epoxide. Data for 1H-NMR methyl chemical shifts are used to show that the epoxide has the mechanistically more plausible 9β,11β configuration. Thus, D-2 is 9β,11β-epoxy-16β-methyl-1,4-pregnadiene-17α,21-diol-3,20-dione, and D-3 is its corresponding 21-propanoate. The various enzyme-catalyzed and nonenzyme-catalyzed reactions involved in the degradation of beclomethasone dipropionate in human plasma are discussed. A degradation scheme is proposed. The American Society for Pharmacology and Experimental Therapeutics ER -