INDENTIFICATION OF MAJOR URINARY METABOLITES OF ACNU, 3-[(4-AMINO-2-METHYL-5-PYRIMIDINYL) METHYL]-1-(2-CHLOROETHYL)-1-NITROSOUREA HYDROCHLORIDE IN RATS

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Metabolites of -[(4-amino-2-methyl-5-pyrimidinyl) methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride (ACNU) in rat urine were investigated. After intravenous administration of ^<14>C-ACNU into rats, four major radioactive metabolites and two minor ones were detected in the urine by two-dimensional thin-layer chromatograhic analysis. The main metablite was identified to be an imidazolidinone compound, 1-[(4-amino-2-methyl-5-pyrimidinyl) methyl]-5-hydroxy-2-imidazolidinone (M-D). One of the other major metabolites was identified to be a nitrosated compound of the main metabolite i.e., 1-[(4-amino-2-methyl-5-pyrimidinyl) methyl]-5-hydroxy-3-nitroso-2-imidazolidinone (M-C). These were new types of metabolites which have not been reported in the metabolic study of other chloroethylnitrosourea derivatieves. Compared with authentic compounds, two metabolites were identified to be a denitrosated derivative of ACNU i.e., 1-[(4-amino-2-methyl-5-pyrimidinyl) methyl]-3-(2-chloroethyl) urea (M-B), and a cyclized pyrimidopyrimidine compound which lacks the ethylene moiety of ACNU, i.e., 3,4-dihydro-7-methylpyrimido [4,5-d] pyrimidin-2-(1 H)-one (M-A). The two minor metabolites were supposed to be compounds derived from M-A. Discussions were made on mechanism of formation of these metabolites in vivo.
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