Review of the bioanalytical methods for the determination of methotrexate and its metabolites in in vitro, preclinical and clinical studies : Case studies and perspectives
Copyright © 2016 John Wiley & Sons, Ltd..
Methotrexate is an old drug that has found use in several therapeutic areas, such as cancer to treat various malignancies, rheumatoid arthtritis and inflammatory bowel disease. Owing to its structural properties of possessing two carboxylic acid groups and having low native fluorescence, it has provided technical challenges for development of bioanalytical methods. Also, in vivo metabolism leading to circulatory metabolites such as 7-hydroxymethotrexate and 2,4-diamino N10 -methylpteroic acid, as well as the formation of polyglutamate metabolites intracellularly have added further complexity for the assays in terms of the analytes that need to be quantified in addition to methotrexate. The present review is aimed at providing a concise tabular summary of chromatographic assays with respect to method nuances including assay/chromatographic conditions, key validation parameters and applicable remarks. Several case studies are reviewed under various subheadings to provide the challenges involved in the method development for methotrexate and metabolites. Finally, a discussion section is devoted to overall perspectives obtained from this review.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2017 |
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Erschienen: |
2017 |
Enthalten in: |
Zur Gesamtaufnahme - volume:31 |
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Enthalten in: |
Biomedical chromatography : BMC - 31(2017), 1 vom: 11. Jan. |
Sprache: |
Englisch |
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Beteiligte Personen: |
Patel, Harilal [VerfasserIn] |
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Links: |
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Anmerkungen: |
Date Completed 18.01.2017 Date Revised 18.01.2017 published: Print-Electronic Citation Status MEDLINE |
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doi: |
10.1002/bmc.3849 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM264295706 |
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520 | |a Methotrexate is an old drug that has found use in several therapeutic areas, such as cancer to treat various malignancies, rheumatoid arthtritis and inflammatory bowel disease. Owing to its structural properties of possessing two carboxylic acid groups and having low native fluorescence, it has provided technical challenges for development of bioanalytical methods. Also, in vivo metabolism leading to circulatory metabolites such as 7-hydroxymethotrexate and 2,4-diamino N10 -methylpteroic acid, as well as the formation of polyglutamate metabolites intracellularly have added further complexity for the assays in terms of the analytes that need to be quantified in addition to methotrexate. The present review is aimed at providing a concise tabular summary of chromatographic assays with respect to method nuances including assay/chromatographic conditions, key validation parameters and applicable remarks. Several case studies are reviewed under various subheadings to provide the challenges involved in the method development for methotrexate and metabolites. Finally, a discussion section is devoted to overall perspectives obtained from this review | ||
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