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

Hansson, Karin LU ; Orrling, Henrik LU ; Blomgren, Anders LU ; Isaksson, Anders LU ; Schliamser, Gloria LU ; Heldrup, Jesper LU and Pronk, Cornelis Jan (2021) In Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences 1186.
Abstract

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... (More)

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.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Acute lymphoblastic leukemia, Folate cycle metabolites, Folinic acid, High-dose methotrexate, MRM, Tandem mass spectrometry
in
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
volume
1186
article number
123007
publisher
Elsevier
external identifiers
  • scopus:85118969523
  • pmid:34781107
ISSN
1570-0232
DOI
10.1016/j.jchromb.2021.123007
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2021 The Authors
id
1745c8c2-e76c-4870-a358-a0427881baf6
date added to LUP
2021-12-02 17:03:27
date last changed
2024-06-17 00:43:00
@article{1745c8c2-e76c-4870-a358-a0427881baf6,
  abstract     = {{<p>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.</p>}},
  author       = {{Hansson, Karin and Orrling, Henrik and Blomgren, Anders and Isaksson, Anders and Schliamser, Gloria and Heldrup, Jesper and Pronk, Cornelis Jan}},
  issn         = {{1570-0232}},
  keywords     = {{Acute lymphoblastic leukemia; Folate cycle metabolites; Folinic acid; High-dose methotrexate; MRM; Tandem mass spectrometry}},
  language     = {{eng}},
  month        = {{12}},
  publisher    = {{Elsevier}},
  series       = {{Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences}},
  title        = {{Simultaneous determination of folate and methotrexate metabolites in serum by LC-MS/MS during high-dose methotrexate therapy}},
  url          = {{http://dx.doi.org/10.1016/j.jchromb.2021.123007}},
  doi          = {{10.1016/j.jchromb.2021.123007}},
  volume       = {{1186}},
  year         = {{2021}},
}