Karami Forough, Ranjbar Sara, Ghasemi Younes, Negahdaripour Manica
Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Central Research Laboratory, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
J Pharm Anal. 2019 Dec;9(6):373-391. doi: 10.1016/j.jpha.2019.06.001. Epub 2019 Jun 20.
Methotrexate (MTX) is a folate antagonist drug used for several diseases, such as cancers, various malignancies, rheumatoid arthritis (RA) and inflammatory bowel disease. Due to its structural features, including the presence of two carboxylic acid groups and its low native fluorescence, there are some challenges to develop analytical methods for its determination. MTX is metabolized to 7-hydroxymethotrexate (7-OH-MTX), 2,4-diamino-N10-methylpteroic acid (DAMPA), and the active MTX polyglutamates (MTXPGs) in the liver, intestine, and red blood cells (RBCs), respectively. Additionally, the drug has a narrow therapeutic range; hence, its therapeutic drug monitoring (TDM) is necessary to regulate the pharmacokinetics of the drug and to decrease the risk of toxicity. Due to environmental toxicity of MTX; its sensitive, fast and low cost determination in workplace environments is of great interest. A large number of methodologies including high performance liquid chromatography equipped with UV-visible, fluorescence, or electrochemical detection, liquid chromatography-mass spectroscopy, capillary electrophoresis, UV-visible spectrophotometry, and electrochemical methods have been developed for the quantitation of MTX and its metabolites in pharmaceutical, biological, and environmental samples. This paper will attempt to review several published methodologies and the instrumental conditions, which have been applied to measure MTX and its metabolites within the last decade.
甲氨蝶呤（MTX）是一种叶酸拮抗剂药物，用于治疗多种疾病，如癌症、各种恶性肿瘤、类风湿性关节炎（RA）和炎症性肠病。由于其结构特征，包括存在两个羧酸基团以及其天然荧光较弱，开发用于测定它的分析方法存在一些挑战。MTX分别在肝脏、肠道和红细胞（RBCs）中代谢为7-羟基甲氨蝶呤（7-OH-MTX）、2,4-二氨基-N10-甲基蝶酸（DAMPA）和活性甲氨蝶呤聚谷氨酸盐（MTXPGs）。此外，该药物的治疗窗较窄；因此，对其进行治疗药物监测（TDM）对于调节药物的药代动力学和降低毒性风险是必要的。由于MTX对环境具有毒性，在工作场所环境中对其进行灵敏、快速且低成本的测定备受关注。已经开发了大量方法，包括配备紫外可见、荧光或电化学检测的高效液相色谱法、液相色谱-质谱法、毛细管电泳法、紫外可见分光光度法和电化学方法，用于定量测定药物、生物和环境样品中的MTX及其代谢物。本文将尝试综述过去十年中已应用于测量MTX及其代谢物的几种已发表方法和仪器条件。
