RT Journal Article SR Electronic T1 Thioguanine Administered as a Continuous Intravenous Infusion to Pediatric Patients Is Metabolized to the Novel Metabolite 8-Hydroxy-Thioguanine JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 870 OP 874 VO 291 IS 2 A1 Brenda J. Kitchen A1 Asher Moser A1 Elizabeth Lowe A1 Frank M. Balis A1 Brigitte Widemann A1 Lawrence Anderson A1 John Strong A1 Susan M. Blaney A1 Stacey L. Berg A1 Michelle O’Brien A1 Peter C. Adamson YR 1999 UL http://jpet.aspetjournals.org/content/291/2/870.abstract AB Thiopurine antimetabolites have been in clinical use for more than 40 years, yet the metabolism of thiopurines remains only partially understood. Data from our previous pediatric phase 1 trial of continuous i.v. infusion of thioguanine (CIVI-TG) suggested that TG was eliminated by saturable mechanism, with conversion of the drug to an unknown metabolite. In this study we have identified this metabolite as 8-hydroxy-thioguanine (8-OH-TG). The metabolite coeluted with the 8-OH-TG standard on HPLC and had an identical UV spectrum, with a λmax of 350 nm. On mass spectroscopy, the positive ion, single quad scan of 8-OH-TG yielded a protonated molecular ion at 184 Da and contained diagnostic ions atm/z 167, 156, 142, and 125 Da. Incubation of TG in vitro with partially purified aldehyde oxidase resulted in 8-OH-TG formation. 8-OH-TG is the predominant circulating metabolite found in patients receiving CIVI-TG and is likely generated by the action of aldehyde oxidase. U.S. Government