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Presence of 2,4‐diamino‐N 10 ‐methylpteroic acid after high‐dose methotrexate
Author(s) -
Donehower Ross C.,
Hande Kenneth R.,
Drake James C.,
Chabner Bruce A.
Publication year - 1979
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt197926163
Subject(s) - methotrexate , chemistry , radioimmunoassay , dihydrofolate reductase , urine , antifolate , chromatography , pharmacology , carboxypeptidase , antimetabolite , enzyme , biochemistry , medicine
Assay of plasma methotrexate has been established as important to its safe use. We have investigated the specificity of 2 assay procedures for methotrexate: the competitive dihydrofolate reductase binding assay (CRBA) and the radioimmunoassay (RIA). The RIA of plasma methotrexate resulted in consistently higher values than the CRRA, with greater differences at later measurement times. A compound that strongly cross‐reacts in the RIA, but not the CRBA, has been identified in plasma and urine of patients on high‐dose methotrexate therapy, and appears to be the carboxypeptidase cleavage product (2,4‐diamino‐N 10 ‐methylpteroic acid) on the basis of chromatographic and ultraviolet spectral properties. Although this compound is present as a minor contaminant in commercial methotrexate preparations, quantitative assessment of urinary excretion suggests that in man a major portion of the compound is derived from methotrexate metabolism.