Detection and identification of 6-methylmercapto-8-hydoxypurine, a major metabolite of 6-mercaptopurine, in plasma during intravenous administration.
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| Abstract |
6-Mercaptopurine, a hypoxanthine antimetabolite, is used in the treatment of acute lymphoblastic leukemia (ALL) in children. Extensively metabolized before it exerts cytotoxic action, it is catabolized into 6-mercapto-2,8-dihydroxypurine (thiouric acid), which is excreted by the kidneys. We describe a metabolite of 6-mercaptopurine, 6-methylmercapto-8-hydroxypurine, whose presence has not been previously reported in plasma. This compound was found in high concentrations in plasma during high-dose 6-mercaptopurine infusions (1300 mg/m2 in 24 h). This previously unknown compound was identified by reversed-phase HPLC with absorbance detection and by gas chromatography-mass spectrometry. The pathways leading to 6-methylmercapto-8-hydroxypurine in vivo are not yet fully understood. In a group of 17 patients treated with four courses of high-dose 6-mercaptopurine infusions according to the ALL-8 treatment protocol of the Dutch Childhood Leukemia Study Group, the steady-state concentrations of 6-methylmercapto-8-hydroxypurine in plasma were one-fifth of the parent drug concentrations, with wide interindividual variation. The formation of high concentrations of 6-methylmercapto-8-hydroxypurine in plasma, especially during the infusion, probably indicates another catabolic pathway of high-dose 6-mercaptopurine, apart from its conversion into thiouric acid.
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| Authors | C W Keuzenkamp-Jansen, J M van Baal, R A De Abreu, J G de Jong, R Zuiderent, J M Trijbels |
| Journal | Clinical chemistry (Clin Chem) Vol. 42 Issue 3 Pg. 380-6 (Mar 1996) ISSN: 0009-9147 [Print] England |
| PMID | 8598099 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Chemical References |
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