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Improved methods for determining the concentration of 6-thioguanine nucleotides and 6-methylmercaptopurine nucleotides in blood.
Reversed-phase high-performance liquid chromatographic approach to determine total lymphocyte concentrations of 6-thioguanine, methylmercaptopurine and methylthioguanine in humans.
We chose the basic assay (2) for three reasons: (a) this procedure has been routinely used in our laboratory for many years; (b) there is good comparison between the 6-thioguanine nucleotide (6-TGN) concentrations measured with both procedures (unpublished own observations); and (c) 6-TGNs are considered the active thiopurine metabolites, whereas the role of 6-methyl-mercaptopurine for therapeutic drug monitoring is still a matter of debate (except for compliance).
Quantitation of 6-thioguanine in peripheral blood leukocyte DNA in Crohn's disease patients on maintenance 6-mercaptopurine therapy.
Thiopurine Smethyltransferase activity in human erythrocytes: a new HPLC method using 6-thioguanine as substrate.
If patients with a homozygous deficiency of TPMT are given thiopurine derivatives at a standard therapeutic oral dosage, 6-thioguanine nucleotides will accumulate, usually within 4-6 weeks, to toxic concentrations.
High-performance liquid chromatographic assay of the methyl and nucleotide metabolites of 6-mercaptopurine: quantification of red blood cell 6-thioguanine nucleotide, 6-thioinosinic acid and methylmercaptopurine metabolites in a single sample.
3) This anabolic route leading to 6-thioguanine nucleotides (6-TGNs) is in competition in red blood cells (RBCs) with methylation of 6-TIMP into methyl 6-TIMP (Me6-TEMP) via thiopurine S-methyltransferase (TPMT), a cytosolic, S-adenosyl methionine-dependent enzyme.
Differential chromatid damage induced by 6-thioguanine in CHO cells.
6-MP is further converted in the liver and gut to 6-thioguanine nucleotides, the pharmacologically active metabolites, by several enzymes, including hypoxanthine guanine phosphoribosyltransferase.