The stability of trifluorothymidine: hydrolysis in buffered aqueous solutions

The decomposition of trifluorothymidine in aqueous solution, and borate and phosphate buffers has been studied using an h.p.l.c. method. In aqueous solution accelerated studies demonstrate that a storage life, to 10% loss, of more than 30 years at 4 degrees C is predicted, but steam sterilization causes extensive breakdown. Considerable differences occur in the kinetics and routes of decomposition in borate and phosphate buffers in the pH range 4-8. Hydroxide ion attack producing 5-carboxy-2'-deoxyuridine is suppressed in borate buffers. Complex kinetics of decomposition in phosphate buffer are found and possible explanations suggested. Steam sterilization in buffered solution also leads to unacceptable breakdown.