Stability and compatibility studies of zorubicin in intravenous fluids and PVC infusion bags

The stability of zorubicin (ZOR) in admixtures for continuous intravenous infusion was studied. ZOR was reconstituted and diluted to 600 mu g ml(-1) for simulated infusion and to 250 and 1000 mu g ml(-1) for storage in poly(vinyl chloride) (PVC) bags containing 5% dextrose injection or 0.9%, sodium chloride injection (0.9% NaCl). Bags were then stored at refrigerated temperature (4 degrees C) and in the dark for 24 h. ZOR concentrations in each admixture were tested by stability-indicating high-performance liquid chromatographic (HPLC) assay with ultraviolet detection. No substantial loss of ZOR was observed during simulated infusions (n = 4) using PVC infusion bags and administration sets over a 1 h infusion. The drug stored at 4 degrees C in the dark in PVC bags showed that it is highly unstable at 250 mu g ml(-1) in 0.9% NaCl injection and in 5% dextrose injection. On the other hand, under the same storage conditions, at 1000 mu g ml(-1); ZOR is more stable in 0.9% NaCl injection (6 h) than in 5% dextrose (4 h). The reported superior stability of the 1000 mu g ml(-1) in 0.9% NaCl can be explained, at least in part, by the difference in pH. Changes in pH, particularly a decrease, seem to affect adversely the stability of ZOR. In fact, ZOR is rapidly converted into daunorubicin, the dominant degradation product, which is more cardiotoxic than the parent drug. Therefore, several precautions must be observed when the commercial product (Rubidazone) is prepared and reconstituted in i.v. fluids and containers.