URINARY STABILITY OF CARBOXYCYCLOPHOSPHAMIDE AND CARBOXYIFOSFAMIDE, 2MAJOR METABOLITES OF THE ANTICANCER DRUGS CYCLOPHOSPHAMIDE AND IFOSFAMIDE

Phosphorus-31 nuclear magnetic resonance spectroscopy was used to eval uate the stability of carboxycyclophosphamide (CXCP) and carboxyifosfa mide (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 (approximate to 10% degradation in 24 h). I n contrast, they are much less stable at pH 5.5 (approximate to 80% de gradation of CXIF and approximate to 50% degradation of CXCP in 24 h). The rate of degradation of CXCP and CXIF was a function of the storag e temperature of the urine samples but, even at -80 degrees C, was not negligible. approximate to 30% degradation for CXCP irrespective of p H and approximate to 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 deg rees, -20 degrees, or -80 degrees C) of the urine samples. CXCP and CX IF 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 degr ees C. To ensure a true estimate of CXCP and CXIF levels, urine sample s must be frozen and stored at -80 degrees C within a few hours of mic turition. CXCP and CXIF assays should also be carried out within 2 mon ths and 1 month of storage, respectively.