BCNU stability as a function of ethanol concentration and temperature

BCNU is increasingly used in low ethanol (ETOH) concentrations, 5% dextrose-water (D5W), or normal saline (NS) solutions, especially for intra-arterial and prolonged (e.g., 3 day) intravenous (IV) infusions. Little work, however, has been done to evaluate BCNU decomposition rates in concentrations, diluents, and temperatures similar to those employed clinically. This study examined BCNU solutions in ETOH, NS, and D5W to evaluate, conclusively, initial recovery and decomposition rates in these three diluents. Initial BCNU recovery rates were: 95.6 ± 0.3% (100% D5W), 89.6 ± 0.5% (15% ETON), and 85.2 ± 0.5% (NS) (P < 0.001). Study of all solutions revealed no measurable BCNU decomposition over 24 hrs (0° C) and no significant difference in decomposition rates between any of the diluents (19.5° C). At 37° C, the solutions showed different half-lives: 14.3 ± 0.19 hrs (15% ETOH), 10.6 ± 0.02 hrs (10% ETON), 8.2 ± 0.21 hrs (5% ETOH), 7.3 ± 0.06 hrs (NS), and 6.8 ± 0.07 hrs (D5W) (P < 0.001). Decomposition rates between all three temperatures (19.5° C, 37° C, and 50° C) were significantly different (P < 0.01) for each diluent. Dissolving BCNU powder into either D5W or NS required only 5 min when hand-shaken at body temperature. This study of initial recovery and decomposition rates suggests that, although BCNU decomposition rates were significantly increased at body temperature (37° C), it was quite low and essentially unaffected by different diluents at room temperature (i.e., 19.5°C). D5W as a diluent for BCNU appeared to provide significantly higher recovery than NS or 15% ETON with no significant difference in half-life at room temperature and thus appeared a practical alternative diluent to ETOH for infusions.