PT  - JOURNAL ARTICLE
AU  - Kuncoro Foe
AU  - H.T. Andrew Cheung
AU  - Bruce N. Tattam
AU  - Kenneth F. Brown
AU  - J. Paul Seale
TI  - Degradation Products of Beclomethasone Dipropionate in Human Plasma
DP  - 1998 Feb 01
TA  - Drug Metabolism and Disposition
PG  - 132--137
VI  - 26
IP  - 2
4099  - http://dmd.aspetjournals.org/content/26/2/132.short
4100  - http://dmd.aspetjournals.org/content/26/2/132.full
SO  - Drug Metab Dispos1998 Feb 01; 26
AB  - 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