Simultaneous determination of folate and methotrexate metabolites in serum by LC-MS/MS during high-dose methotrexate therapy
(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.
(Less)
- author
- Hansson, Karin LU ; Orrling, Henrik LU ; Blomgren, Anders LU ; Isaksson, Anders LU ; Schliamser, Gloria LU ; Heldrup, Jesper LU and Pronk, Cornelis Jan
- organization
- publishing date
- 2021-12-01
- 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}}, }