BACKGROUND: Cyclophosphamide (CYP) is used to treat cancers in combination with mesna to prevent cystitis. The use of extemporaneously prepared admixtures of these drugs must be supported by documentation of their chemical stability. OBJECTIVE: To evaluate the chemical stability of CYP and mesna admixtures in dextrose 5% polyethylene infusion bags. METHODS: The drugs were diluted in 100-mL dextrose 5% infusion bags to final concentrations of CYP 10.8 mg/mL with mesna 3.2 mg/mL (solution A) and CYP 1.8 mg/mL with mesna 0.54 mg/mL (solution B). Six infusion bags from each solution were stored at 4 degrees C and 6 were stored at room temperature. Triplicate HPLC determinations were performed on each bag to measure drug concentrations at 0, 1, 2, 4, 6, 12, 24, 48, and 96 hours. RESULTS: At 96 hours, drug concentrations in all solutions stored at room temperature were found to be <80% compared with the initial concentrations. The solutions stored at 4 degrees C retained at least 90% of the initial drug concentrations at 48 hours. The pH of solutions A and B stored at room temperature decreased significantly by 4.44 and 4.31 units, respectively. The pH of the refrigerated infusion bags decreased significantly by 1.46 units for solution B. CONCLUSIONS: Admixtures stored at 4 degrees C (pH 7.90 +/- 0.004; mean +/- SD) are stable for 48 hours. The CYP and mesna combination can be infused at room temperature over 6 hours without significant degradation of the drugs. Stabilities are dependent on pH, temperature, and/or concentration.
BACKGROUND:Cyclophosphamide (CYP) is used to treat cancers in combination with mesna to prevent cystitis. The use of extemporaneously prepared admixtures of these drugs must be supported by documentation of their chemical stability. OBJECTIVE: To evaluate the chemical stability of CYP and mesna admixtures in dextrose 5% polyethylene infusion bags. METHODS: The drugs were diluted in 100-mL dextrose 5% infusion bags to final concentrations of CYP 10.8 mg/mL with mesna 3.2 mg/mL (solution A) and CYP 1.8 mg/mL with mesna 0.54 mg/mL (solution B). Six infusion bags from each solution were stored at 4 degrees C and 6 were stored at room temperature. Triplicate HPLC determinations were performed on each bag to measure drug concentrations at 0, 1, 2, 4, 6, 12, 24, 48, and 96 hours. RESULTS: At 96 hours, drug concentrations in all solutions stored at room temperature were found to be <80% compared with the initial concentrations. The solutions stored at 4 degrees C retained at least 90% of the initial drug concentrations at 48 hours. The pH of solutions A and B stored at room temperature decreased significantly by 4.44 and 4.31 units, respectively. The pH of the refrigerated infusion bags decreased significantly by 1.46 units for solution B. CONCLUSIONS: Admixtures stored at 4 degrees C (pH 7.90 +/- 0.004; mean +/- SD) are stable for 48 hours. The CYP and mesna combination can be infused at room temperature over 6 hours without significant degradation of the drugs. Stabilities are dependent on pH, temperature, and/or concentration.
Authors: Rachel Kennedy; Daniel Groepper; Michael Tagen; Robbin Christensen; Fariba Navid; Amar Gajjar; Clinton F Stewart Journal: Ann Pharmacother Date: 2010-01-26 Impact factor: 3.154