Abstract

Methotrexate (MTX) is the only chemotherapy drug that is routinely monitored by therapeutic drug monitoring service in Malaysia government hospitals. The patients with MTX plasma concentration exceeding 0.4 μM for 48 h are at higher risk to develop toxicities such as nephrotoxicity, hepatotoxicity, neurotoxicity, mucositis and myelosuppression. The aim of this study was to develop and validate the ultra-high performance liquid chromatography−tandem mass spectrometry (UHPLC−MS/MS) method for MTX quantitation in human serum. Our results show that the retention times of MTX and warfarin (internal standard) were 1.82 and 2.68 min, respectively. The linearity was obtained at the concentrations from 25 to 500 ng/mL with the regression equation of y = 1025x – 11757 and r² of 0.9901. This analyte was stable in a freezer at –80°C for up to 90 days. As a conclusion, this UHPLC−MS/MS method is an optional technique for clinicians to quantitate the patient’s MTX levels in the hospital.

中文翻译：

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高效液相色谱-串联质谱法在人血清中甲氨蝶呤定量分析中的应用

摘要

甲氨蝶呤（MTX）是马来西亚政府医院中由治疗药物监测服务常规监测的唯一化疗药物。MTX血浆浓度超过0.4μM的患者持续48 h出现肾毒性，肝毒性，神经毒性，粘膜炎和骨髓抑制等毒性反应的风险较高。这项研究的目的是开发和验证用于人血清中MTX定量的超高效液相色谱-串联质谱（UHPLC-MS / MS）方法。我们的结果表明，MTX和华法林（内标）的保留时间分别为1.82和2.68分钟。在25至500 ng / mL的浓度下获得线性关系，回归方程为y = 1025x – 11757和r ²为0.9901。该分析物在–80°C的冰箱中稳定达90天。结论是，此UHPLC-MS / MS方法是临床医生用来量化患者在医院中MTX水平的一种可选技术。