Identification of 6-Methylmercaptopurine Ribonucleoside 5′-Diphosphate and 5′-Triphosphate as Metabolites of 6-Mercaptopurine in Man Free

Acid-soluble extracts of bone marrow and blood samples from leukemia patients receiving 6-mercaptopurine were analyzed by anion-exchange high-pressure liquid chromatography. This has led to the identification of two previously unrecognized metabolites of 6-mercaptopurine, 6-methylmercaptopurine ribonucleoside 5′-diphosphate and the corresponding 5′-triphosphate. Intracellular concentrations of 6-methylmercaptopurine ribonucleoside 5′-triphosphate often exceeded those of either the corresponding 5′-mono- or 5′-diphosphate and were estimated to be as high as 145 μm. There is no evidence at present that these newly reported metabolites of 6-mercaptopurine are themselves highly cytotoxic, but they may perhaps contribute to the overall cytotoxicity of 6-mercaptopurine.