Analytical interference in the therapeutic drug monitoring of methotrexate

Ann Biol Clin (Paris). 2016 Jun 1;74(3):333-7. doi: 10.1684/abc.2016.1135.

Abstract

High-dose of methotrexate chemotherapy is used in the treatment of some tumors. It presents several side effects that required therapeutic drug monitoring, which is commonly performed on 24, 48 and 72h after the beginning of the methotrexate infusion. Treatment of overexposure to methotrexate is based on injection of carboxypeptidase G2, which specifically degrades methotrexate into inactive metabolite: DAMPA. FPIA immunoassay on TDx automated analyzer (Abbott™) was used for therapeutic drug monitoring of methotrexate. This immunoassay presented a significant cross-reactivity between methotrexate and DAMPA, which widely overestimate the residual concentration compared to the gold standard HPLC/MS. TDx automated analyzer was substituted by a new immunoassay on Architect automated analyzer (Abbott™). However, this immunoassay has the same cross-reactivity, which needs to be careful when monitoring methotrexate after an injection of carboxypeptidase G2. In order to determine the most suitable assay for the therapeutic drug monitoring of methotrexate, the knowledge of injection of carboxypeptidase G2 remains essential.

Keywords: carboxypeptidase G2; cross reactivity; methotrexate; osteosarcoma.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Bone Neoplasms / blood
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / metabolism
  • Contraindications
  • Cross Reactions
  • Drug Monitoring* / instrumentation
  • Drug Monitoring* / methods
  • Drug Monitoring* / standards
  • Drug Substitution
  • Fluorescence Polarization Immunoassay / methods
  • Humans
  • Kidney Diseases / chemically induced
  • Kidney Diseases / metabolism
  • Male
  • Methotrexate / pharmacokinetics*
  • Methotrexate / therapeutic use*
  • Osteosarcoma / blood
  • Osteosarcoma / drug therapy*
  • Osteosarcoma / metabolism

Substances

  • Methotrexate