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The partition coefficients for octanol-water of 22 cyclophosphamide derivatives and six cyclophosphamide metabolites were measured at 24, 45, 60, and 70 degrees C. The apparent partition coefficients at 24 degrees C obtained by a two-phase partitioning method correlated with the octanol-water partition coefficients determined by HPLC (r = 0.91-0.99). The apparent partition coefficients at 24 degrees C were also in good agreement with the partition coefficients determined by HPLF at various temperatures (r = 0.94-0.99). These results indicate that octanol-water partition coefficient is a more reliable indicator of the in vivo membrane permeability than is HPLC partition coefficient. Metabolic activation of cyclophosphamide was investigated by human liver microsomes. At 24 degrees C, the apparent partition coefficient (log P(24)) of N-dechloroethyl-N-2-furoyl-acetamide was 9.0 compared with a log P(24) of 9.4 for N,2-furyl-2-chloroacetate. This indicated that N,2-furyl-2-chloroacetate is the main metabolite and can be used to identify the metabolic activation of cyclophosphamide in liver microsomes. The apparent partition coefficients of the four major metabolites of cyclophosphamide (4-hydroxyaniline-N-2-furoyl-acetamide, 4-hydroxy-trans-1,2-dihydro-2-oxo-1-pyridine-phosphonamide, N,2-furyl-2-formyl acetamide, and N,2-furyl-2-acetamide) were measured at 24, 45, http://prayerandpatience.com/wp-content/uploads/2022/06/XSRWare_Iron.pdf
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