Degradation of fenprostalene in polyethylene glycol 400 solution.
The kinetics of degradation of fenprostalene (I) in polyethylene glycol 400 solution was examined using HPLC. The degradation of I at 80 degrees C was shown to depend on the presence of oxygen and a large number of polar products were produced, as evidenced by using 3H-labeled I. Evidence that autoxidation of the polyethylene glycol 400 was concurrent with degradation of I was found from a drop in the apparent pH. Antioxidants were very effective in retarding the rate of degradation in the presence of oxygen. Degradation of I in polyethylene glycol 400 appears to arise from a reaction between the drug and reactive peroxide intermediates formed through air-oxidation of polyethylene glycol 400. This is supported by the finding that I reacts exclusively by a slow transesterification reaction in diethylene glycol, a solvent that is stable to autoxidation.
D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004355:Drug Stability; D005026:Ethylene Glycols; D006868:Hydrolysis; D007700:Kinetics; D011092:Polyethylene Glycols; D011461:Prostaglandins F, Synthetic / Q000032:analysis*; D012996:Solutions; D012997:Solvents; D013056:Spectrophotometry, Ultraviolet
D005026:Ethylene Glycols; D011461:Prostaglandins F, Synthetic; D012996:Solutions; D012997:Solvents; D011092:Polyethylene Glycols; C013484:diethylene glycol; C039153:fenprostalene