Stability of trimethoprim-sulfamethoxazole injection in two infusion fluids

The concentrations over time of trimethoprim (TMP) and sulfamethoxazole (SMZ) in solution after preparations of admixtures of TMP-SMZ in 5% dextrose injection (D5W) and in 0.9% sodium chloride injection (NS) were measured. Admixtures (50 ml) containing three TMP concentrations (0.64 mg/ml, 1.6 mg/ml, and 3.2 mg/ml) and three SMZ concentrations (3.2 mg/ml, 8.0 mg/ml, and 16 mg/ml) were prepared in D5W or NS, representing 1:25 v/v, 1:10 v/v, and 1:5 v/v dilutions of TMP-SMZ injection, respectively. Aliquots of each admixture were obtained immediately upon dilution and after 0.5, 1, 2, 4, 8, and 24 hours. The aliquots were filtered and assayed for TMP and SMZ by high-pressure liquid chromatography. Each mixture was inspected visually for any changes in clarity or color, and the pH of each admixture was measured over time. The concentration of SMZ in all admixtures remained constant over 24-hour study period. The TMP concentration did not change significantly (less than 10% of initial concentration) after 1:25 v/v dilutions in either D5W or NS for up to four hours. With a dilution of 1:10 v/vv D5W TMP was stable at D5W for up to two hours. TMP precipitated rapidly in dilutions of 1:5 v/v in either D5W or NS. The pH of the admixtures ranged from 9.39 to 10.10. D5W is the preferred diluent for TMP-SMZ injection if a dilution ratio of 1:10 v/v is desired. Either D5W or NS may be used if a dilution ratio of 1:25 v/v is desired.