Analytical Sciences

Methotrexate Polyglutamates Analysis by Chromatography Methods in Biological Matrices: A Review

Yiming ZHANG,*,** Liyu SUN,*,** Libo ZHAO,**,*** Xiaoling WANG,**,*** Zhigang ZHAO,*,** and Shenghui MEI*,**

*Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, 119 Nansihuan West Road, Fengtai District, Beijing 100070, P. R. China
**Department of Clinical Pharmacology, College of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, P. R. China
***Department of Pharmacy, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing 100045, P. R. China

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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