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Therapeutic Drug Monitoring of Methotrexate in Plasma Using Ultra High-Performance Liquid Chromatography–Electrospray Ionization–Tandem Mass Spectrometry: Necessary After Administration of Glucarpidase in Methotrexate Intoxications

Mulder, Midas B., PharmD*; Huisman, Ruud*; Engels, Frederike K., PharmD, PhD; van der Sluis, Inge M., MD, PhD; Koch, Birgit C. P., PharmD, PhD*

doi: 10.1097/FTD.0000000000000515
Grand Rounds

Abstract: High-dose methotrexate (HD-MTX) is used to treat a variety of cancers. In all patients receiving HD-MTX, plasma MTX levels are monitored mainly to anticipate rescue therapy to prevent adverse events. We present 2 children treated with HD-MTX and afterward treated with glucarpidase at different time-points after their HD-MTX infusions. After the administration of glucarpidase, a nontoxic metabolite of MTX cross-reacts with MTX in the standard immunoassay (Abbott Diagnostics, Hoofddorp, the Netherlands) resulting in an artificially elevated MTX level. An artificially elevated MTX level results in unnecessarily long folinic acid administration, which decreases the effectivity of MTX. This grand round highlights the importance of measuring plasma MTX levels after the administration of glucarpidase with an ultra high-performance liquid chromatography–electrospray ionization–tandem mass spectrometry method instead of with an immunoassay.

*Department of Pharmacy, Erasmus University Medical Center;

Department of Pharmacy, Sophia Children's Hospital, Erasmus University Medical Center; and

Department of Pediatric Haemato-Oncology, Sophia Children's Hospital Rotterdam, Erasmus University Medical Center, the Netherlands.

Correspondence: Midas B. Mulder, PharmD, Department of Pharmacy, Erasmus University Medical Center, PO Box 2040, CA 3000, Rotterdam, Netherlands (e-mail:

The authors declare no conflict of interest.

Received October 04, 2017

Accepted March 29, 2018

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