Interferencia por ácido 2,4-diamino-N10-metilpteroico en la determinación de metotrexato tras la administración de glucarpidasa

Nazaret del Amo del Arco , Raquel Ramos Corral , Javier López Flores , Yessika M. Amezquita Orjuela , Alicia Roldán Pérez , Fernando Cava Valenciano
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引用次数: 1

Abstract

High-dose methotrexate (MTX) treatment involves close monitoring of drug level in order to confirm its proper elimination. One of the possible side effects of this therapy is renal failure, causing accumulation of the drug, and therefore is a mayor toxic effect. Glucarpidase (carboxypeptidase-G2 or CPDG2) is a recombinant enzyme used to reduce MTX serum levels in patients who develop acute renal failure during high-dose MTX treatment. The enzyme reduces MTX concentration by 95-99% within 15-30 minutes after the dose. Glucarpidase cleaves MTX into glutamate and 2,4-diamino-N10-methylpteroic acid, a minor and non-active metabolite. Cross-reactivity of 2,4-diamino-N10-methylpteroic acid in immunological assays of MTX has been previously reported, and is said to cause an enormous overestimation in serum MTX analysis. However immunoassay is a widely used technique for MTX analysis, being the main method for its determination in most clinical laboratories.

An interference case report is presented and MTX analysis in serum samples by liquid chromatography coupled with Ultra-High Resolution Q-Time of Flight Mass Spectrometry (LC-UHR-QTOF) is described.

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大剂量甲氨蝶呤(MTX)治疗包括密切监测药物水平,以确认其适当消除。这种疗法的一个可能的副作用是肾功能衰竭,引起药物的积累,因此是主要的毒性作用。葡糖苷酶(羧肽酶g2或CPDG2)是一种重组酶,用于降低在大剂量MTX治疗期间发生急性肾衰竭的患者的MTX血清水平。该酶在给药后15-30分钟内将MTX浓度降低95-99%。葡萄糖苷酶将MTX切割成谷氨酸和2,4-二氨基- n10 -甲基翼鸟酸,这是一种次要的非活性代谢物。2,4-二氨基- n10 -甲基翼鸟酸在MTX免疫分析中的交叉反应性已经有报道,据说在血清MTX分析中导致了巨大的高估。然而,免疫分析法是广泛应用于MTX分析的技术,是大多数临床实验室检测MTX的主要方法。本文报道了一例干扰病例,并描述了液相色谱-超高分辨率飞行时间质谱(LC-UHR-QTOF)联用分析血清样品中MTX的方法。
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