Stability of AG337, A Thymidylate Synthase Inhibitor, in PVC Infusion Bags

Abstract The stability of AG337, a selective thymidylate synthase inhibitor, in 5% Dextrose in Water (D5W) PVC infusion bags and sodium bicarbonate treated D5W infusion bags was studied at 30°C for seven days. AG337 Solution for Injection, 2% was diluted in D5W infusion bags to yield final AG337 concentrations of 4 mg/mL, 1 nig/mL and 0.1 mg/mL. For the sodium bicarbonate treated D5W infusion bags, the final concentrations of AG337 used were 4 mg/mL, 1 mg/niL and 0.2 mg/mL. The bags were prepared in triplicate and stored at 30°C. At predetermined time intervals, each bag was visually examined for presence of precipitates and samples were withdrawn for HPLC assay and pH testing. No precipitation was observed in any of the samples. The pH of the sodium bicarbonate treated D5W infusion bags remained constant throughout the study. The recovery of AG337 was greater than 93% in all samples tested. The recovery of methyl and propylparaben, used as preservatives in the formulation, however, decreased over time probably due to adsorption in the PVC bags. This study demonstrated that AG337 was stable at 30°C for up to seven days, in D5W infusion bags and in the presence of sodium bicarbonate treated D5W infusion bags.