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Simultaneous determination of folate and methotrexate metabolites in serum by LC-MS/MS during high-dose methotrexate therapy.
Hansson, Karin; Orrling, Henrik; Blomgren, Anders; Isaksson, Anders; Schliamser, Gloria; Heldrup, Jesper; Pronk, Cornelis Jan.
Afiliação
  • Hansson K; Department of Clinical Chemistry and Pharmacology, Lund University, Sweden.
  • Orrling H; Childhood Cancer Centre, Skåne University Hospital, Lund, Sweden.
  • Blomgren A; Department of Clinical Chemistry and Pharmacology, Lund University, Sweden.
  • Isaksson A; Department of Clinical Chemistry and Pharmacology, Lund University, Sweden.
  • Schliamser G; Department of Clinical Chemistry and Pharmacology, Lund University, Sweden.
  • Heldrup J; Childhood Cancer Centre, Skåne University Hospital, Lund, Sweden.
  • Pronk CJ; Childhood Cancer Centre, Skåne University Hospital, Lund, Sweden; Division of Molecular Hematology and Stem Cell Centre, Lund University, Lund, Sweden; Wallenberg Center for Molecular Medicine, Lund University, Lund, Sweden. Electronic address: kees-jan.pronk@med.lu.se.
Article em En | MEDLINE | ID: mdl-34781107
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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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Metotrexato / Cromatografia Líquida / Espectrometria de Massas em Tandem / Leucemia-Linfoma Linfoblástico de Células Precursoras / Ácido Fólico / Antineoplásicos Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Metotrexato / Cromatografia Líquida / Espectrometria de Massas em Tandem / Leucemia-Linfoma Linfoblástico de Células Precursoras / Ácido Fólico / Antineoplásicos Idioma: En Ano de publicação: 2021 Tipo de documento: Article