Kumar Vikram S, Law Terence, Kellogg Mark
Department of Laboratory Medicine, Children's Hospital Boston, Boston, MA, USA.
Methods Mol Biol. 2010;603:359-63. doi: 10.1007/978-1-60761-459-3_34.
Medications that have a narrow therapeutic window must be regularly monitored to assist in clinical dosing. Methotrexate (MTX) is one such chemotherapeutic agent that is closely monitored using various standard assays. Patients who have renal failure and who are treated using high-dose protocols are often given carboxypeptidase-G2 (CPDG(2)) as a chemoprotective agent. In this setting an inactive metabolite of MTX, 2, 4-diamino-N(10)-methylpteroic acid (DAMPA) is produced. DAMPA cross-reacts with MTX in most immunoassays, thus making them unsuitable for the monitoring of MTX in the setting of CPDG(2) therapy. We describe a rapid LC-MS-MS method that can be used to determine MTX levels in these cases.
治疗窗狭窄的药物必须定期监测,以辅助临床给药。甲氨蝶呤(MTX)就是这样一种化疗药物,需使用各种标准检测方法进行密切监测。肾衰竭患者以及采用高剂量方案治疗的患者,常给予羧肽酶-G2(CPDG(2))作为化学保护剂。在这种情况下,会产生MTX的一种无活性代谢物,即2,4-二氨基-N(10)-甲基蝶酸(DAMPA)。在大多数免疫分析中,DAMPA会与MTX发生交叉反应,因此这些免疫分析不适用于监测CPDG(2)治疗情况下的MTX。我们描述了一种快速液相色谱-串联质谱法,可用于测定这些情况下的MTX水平。