Stability of aspirin in different media.

Aspirin rapidly hydrolyzes in various aqueous, organic, and biological media. The purpose of this investigation was to study the decomposition of aspirin in the media that comes in contact with it during analysis in biological fluids for pharmacokinetic studies. These media included water, water-polyethylene glycol 400, water-methanol-acetic acid, phosphate buffer, freshly drawn blood and plasma from control rats and rats deprived of water for 36 hr, and blood precipitated with acetonitrile. Studies were also conducted to determine the decomposition as a function of temperature and pH. Of the various solvent systems studied, aspirin was found most stable in water-polyethylene glycol (4:1, v/v),which provides an excellent medium for preparation of intravenous dosage forms. Phosphate buffer showed significant catalysis of aspirin hydrolysis. A more than fivefold increase in the hydrolysis of aspirin was noted when the temperature was raised to 37 degrees from 22.5 degrees. The hydrolysis of aspirin in rat blood was 13 times faster than that in plasma, with an average half-life in blood of approximately 13 min. This creates significant problems in aspirin disposition kinetic studies. Mixing the blood sample immediately after collection with twice the volume of acetonitrile and thn en centrifuging gives a plasma-acetonitrile mixture in which no lysis of blood cells is observed.