Urinary stability of carboxycyclophosphamide and carboxyifosfamide, two major metabolites of the anticancer drugs cyclophosphamide and ifosfamide.

Abstract

Phosphorus-31 nuclear magnetic resonance spectroscopy was used to evaluate the stability of carboxycyclophosphamide (CXCP) and carboxyifosfamide (CXIF) in human urine at pH 7.0 and 5.5 at 25 degrees, 8 degrees, -20 degrees, and -80 degrees C. At 25 degrees C and pH 7.0, CXCP and CXIF are relatively stable (approximately 10% degradation in 24 h). In contrast, they are much less stable at pH 5.5 (approximately 80% degradation of CXIF and approximately 50% degradation of CXCP in 24 h). The rate of degradation of CXCP and CXIF was a function of the storage temperature of the urine samples but, even at -80 degrees C, was not negligible: approximately 30% degradation for CXCP irrespective of pH and approximately 40% and 50% degradation for CXIF at pH 7.0 and 5.5, respectively, after storage for 6 months. CXCP was more stable than CXIF at either pH (7.0 or 5.5) and at all storage temperatures (8 degrees, -20 degrees, or -80 degrees C) of the urine samples. CXCP and CXIF were more stable at pH 7.0 than at pH 5.5, although this difference fell with decreasing temperatures to be almost negligible at -80 degrees C. To ensure a true estimate of CXCP and CXIF levels, urine samples must be frozen and stored at -80 degrees C within a few hours of micturition. CXCP and CXIF assays should also be carried out within 2 months and 1 month of storage, respectively.