Decomposition of beclomethasone propionate esters in human plasma.
The kinetics of decomposition of beclomethasone dipropionate (BDP), the 17-monopropionate ester (17-BMP), and beclomethasone (BOH) were characterized in whole human plasma (HP), pH 7.1, and in solutions of 1% human serum albumin (HSA), pH 7.4, and 0.067 M phosphate buffer, pH 7.4 (mu = 0.17). A reversed-phase, high-performance liquid chromatography (HPLC) assay enabled simultaneous separation and quantification of beclomethasone propionate esters and six degradation products including three unidentified products, D1-D3, not previously reported. Following incubation of BDP, products were formed in the following sequence, D1, 17-BMP, beclomethasone-21-monopropionate (21-BMP), D3, BOH, and D2. Following incubation of 17-BMP, the same sequence of degradation products was formed with the exception of D1. Following incubation of BOH, only D2 was formed. The decomposition reactions of BDP, 17-BMP, and BOH in HP exhibit pseudo-first-order kinetics. However the degradation reactions of BDP in solutions of 1% HSA and phosphate buffer were found to follow pseudo-zero-order kinetics. At an initial concentration of 40 micrograms mL-1, the half-lives for BDP, 17-BMP, and BOH in HP were 10.9 +/- 0.4, 3.0 +/- 0.2 and 24.8 +/- 0.2 h, respectively.
Foe
K
K
Department of Pharmacy, University of Sydney, Australia. kenb@pharm.usyd.edu.au
Brown
K F
KF
Seale
J P
JP
D000418:Albumins / Q000378:metabolism; D001507:Beclomethasone / Q000031:analogs & derivatives* / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D004950:Esterases / Q000737:chemistry; D006207:Half-Life; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D011485:Protein Binding; D012995:Solubility; D012996:Solutions
D000418:Albumins; D012996:Solutions; C065857:beclomethasone 17-monopropionate; D004950:Esterases; D001507:Beclomethasone