Simultaneous determination of folate and methotrexate metabolites in serum by LC-MS/MS during high-dose methotrexate therapy

Karin Hansson, Henrik Orrling, Anders Blomgren, Anders Isaksson, Gloria Schliamser, Jesper Heldrup, Cornelis Jan Pronk

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

Sammanfattning

High-dose methotrexate (HDMTX) is a central component in the treatment of acute lymphoblastic leukemia, osteosarcoma, and some lymphomas and brain tumors. MTX is given at lethal doses and then is followed by rescue treatment with folinic acid (FA). Despite FA rescue, many patients suffer severe toxicity. The pharmacokinetics of FA rescue have not been sufficiently studied. However, optimization of FA rescue could potentially increase anti-tumor effects, whilst decreasing organ toxicity. Here, we describe our efforts to establish and optimize a liquid chromatography tandem mass spectrometric (LC-MS/MS) method for the simultaneous determination of five essential components of the folate cycle, as well as MTX and its two metabolites. The method was applied to 6 individual patients receiving HDMTX, with 3 or 4 measurements for each patient. The method allows analysis of samples that were initially frozen. This notion, together with the test results in the 6 pilot patients, shows the feasibility of this method to study MTX and FA pharmacokinetics during HDMTX treatment. The method has the potential to optimize HDMTX and FA rescue treatment in individual patients.

Originalspråkengelska
Artikelnummer123007
TidskriftJournal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
Volym1186
DOI
StatusPublished - 2021 dec 1

Bibliografisk information

Publisher Copyright:
© 2021 The Authors

Ämnesklassifikation (UKÄ)

  • Farmakologi och toxikologi
  • Analytisk kemi

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