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Clinical Chemistry 42: 380-386, 1996;
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Clinical Chemistry, Vol 42, 380-386, Copyright © 1996 by American Association for Clinical Chemistry

Detection and identification of 6-methylmercapto-8-hydoxypurine, a major metabolite of 6-mercaptopurine, in plasma during intravenous administration

CW Keuzenkamp-Jansen, JM van Baal, RA De Abreu, JG de Jong, R Zuiderent and JM Trijbels
Center for Pediatric Oncology SE Netherlands, St. Radboud University Hospital Nijmegen, The Netherlands.

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.


The following articles in journals at HighWire Press have cited this article:


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 J. Pharmacol. Exp. Ther.Home page
B. J. Kitchen, A. Moser, E. Lowe, F. M. Balis, B. Widemann, L. Anderson, J. Strong, S. M. Blaney, S. L. Berg, M. O'Brien, et al.
Thioguanine Administered as a Continuous Intravenous Infusion to Pediatric Patients Is Metabolized to the Novel Metabolite 8-Hydroxy-Thioguanine
J. Pharmacol. Exp. Ther., November 1, 1999; 291(2): 870 - 874.
[Abstract] [Full Text]


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