Abstract
Methotrexate (MTX) is used as an immunosuppressant and antineoplastic drug in clinical practice. MTX is a parent drug and converts to MTX polyglutamates (MTXPGs) to exhibit its biological activity. Clinical studies found that MTXPG levels were associated with MTX response and toxicities, especially at low doses. Due to huge variance of MTX response and toxicities between individuals, therapeutic drug monitoring is necessary for its use in individualized therapy. Various chromatography methods coupled with ultraviolet-visible detector, fluorescence detector and mass spectrometry have been reported for MTXPG analysis in various biological matrices. The aim of this paper is to review the chromatographic based methods for the measurement of total and/or individual MTXPGs. We searched Embase, Science Direct and PubMed databases using “methotrexate polyglutamate” and “chromatography” as search terms, and found 745 articles. Of those, 14 articles were extracted for this study. The key steps for method development (sample pretreatment, parameter optimization of liquid chromatography and mass spectrometry, selection of internal standard) and validation (lower limit of quantitation, accuracy, precision, recovery, matrix effect and stability) were analyzed and summarized, which might be helpful for researchers to develop their own methods.
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Acknowledgments
Thanks are given to our patients and nurses. This work was supported by the Beijing Municipal Administration of Hospitals (ZYLX201827), National Key R&D Program of China (2020YFC2008306), and Beijing Municipal Health Bureau (2018000021469G238).
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Xiaoling Wangdid her master’s in pharmacy at Beijing University of Chinese Medicine in 2006. From 2012, she has worked as an office director of child drug use expert committee of the National Health Commission of the People’s Republic of China. She is master tutor and her scientific interests are pediatric clinical pharmacy and pharmacology, pediatric pharmaceutical care, pharmacist education and training.
Zhigang Zhaograduated from the medical department of Peking University in 1990. In 2016, he received a doctorate in clinical pharmacy from the Capital Medical University. He is the director of the department of clinical pharmacy, school of pharmacy, Capital Medical University. He is doctoral supervisor in clinical pharmacology and his scientific interest including clinical pharmacology, clinical pharmacy, and pharmacogenomics.
Shenghui Meigot his doctorate in Capital Medical University in 2011. After graduation, he worked in the department of pharmacy, Beijing Tiantan Hospital. His major work was therapeutic drug monitoring and individualized therapy. His study field including biopharmaceutical analysis, population pharmacokinetic modeling and pharmacogenomics.
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Zhang, Y., Sun, L., Zhao, L. et al. Methotrexate Polyglutamates Analysis by Chromatography Methods in Biological Matrices: A Review. ANAL. SCI. 37, 1655–1664 (2021). https://doi.org/10.2116/analsci.21R001
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DOI: https://doi.org/10.2116/analsci.21R001