Case study—methotrexate toxicity, treatment, and measurement

Abstract Methotrexate (MTX) has long been a critically important chemotherapeutic agent for the treatment of nonmalignant and malignant conditions. At the high-doses typically used for hematologic malignancies, the wide therapeutic index of MTX has made it one of the clearest examples of the advantages of therapeutic drug monitoring aimed at maintaining a drug’s efficacy while reducing the risk of severe toxicities. Here we present a case of high-dose MTX-related multiorgan toxicity that demonstrates critical factors regarding the appropriate administration of MTX, prevention of excessive toxicities, and rescue from toxicities with the use of glucarpidase. Moreover, we review standard assays for therapeutic drug monitoring of MTX and its metabolites and show that liquid chromatography mass spectrometry (LC–MS/MS) for MTX measurements has extremely high sensitivity and specificity, making it an ideal candidate to monitor MTX levels in certain situations.