Analytical interference in the therapeutic drug monitoring of methotrexate.
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.
Laboratoire central de biochimie, Hôpital Robert Debré, CHU de Reims, Reims, France, Laboratoire de biochimie médicale et de biologie moléculaire, UMR CNRS 7369, Faculté de médecine, Reims, France.
Jean-Baptiste
JB
Oudart
Laboratoire central de biochimie, Hôpital Robert Debré, CHU de Reims, Reims, France.
Benjamin
B
Marquet
Laboratoire de pharmacologie et toxicologie, Hôpital Maison Blanche, CHU de Reims, Reims, France, SFR Cap-Santé-EA3801-Université de Reims, Laboratoire de pharmacologie médicale, Faculté de médecine, Reims, France.
Catherine
C
Feliu
Laboratoire de pharmacologie et toxicologie, Hôpital Maison Blanche, CHU de Reims, Reims, France.
Claire
C
Gozalo
Laboratoire de pharmacologie et toxicologie, Hôpital Maison Blanche, CHU de Reims, Reims, France, SFR Cap-Santé-EA3801-Université de Reims, Laboratoire de pharmacologie médicale, Faculté de médecine, Reims, France.
Zoubir
Z
Djerada
Laboratoire de pharmacologie et toxicologie, Hôpital Maison Blanche, CHU de Reims, Reims, France, SFR Cap-Santé-EA3801-Université de Reims, Laboratoire de pharmacologie médicale, Faculté de médecine, Reims, France.
Hervé
H
Millart
D000293:Adolescent; D001859:Bone Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D000075202:Contraindications; D003429:Cross Reactions; D016903:Drug Monitoring / Q000295:instrumentation / Q000379:methods / Q000592:standards; D057915:Drug Substitution; D016231:Fluorescence Polarization Immunoassay / Q000379:methods; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism; D008297:Male; D008727:Methotrexate / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D012516:Osteosarcoma / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism
D008727:Methotrexate
carboxypeptidase G2; cross reactivity; methotrexate; osteosarcoma