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通过LC-MS/MS在血清中同时量化甲甲酸,7-基甲甲酸和肌素,以预测延迟排泄

Yingying Feng¹, Chunzi Li², Wei Xia³

¹Department of Laboratory Medicine, The First Hospital of Jilin University, 1 Xinmin Street, Changchun, Jilin Province 130061, China; College of Medical Technology, Beihua University, Jilin 132013, China.

Journal of pharmaceutical and biomedical analysis

|April 4, 2025

概括

针对儿科急性淋巴细胞白血病 (ALL) 的高剂量甲醇 (HDMTX) 显示出可变的消除. 一种新的LC-MS/MS方法使用血清水平的MTX,7-OHMTX和肌素准确预测延迟的MTX消除,使得及时调整治疗.

科学领域:

药理动力学和药物新陈代谢
分析化学分析化学
儿科瘤学儿科瘤学

背景情况:

高剂量甲状腺素 (HDMTX) 是儿科急性淋巴细胞白血病 (ALL) 治疗的基石.
在HDMTX消除的显著个体间的药理动力学变异可能导致毒性和治疗延迟.
准确及时监测HDMTX及其代谢物对于优化患者的治疗结果至关重要.

研究的目的:

开发和验证一种新的液体染色学-并联质谱法 (LC-MS/MS) 方法,用于同时定量血清甲酸 (MTX),7-基甲酸 (7-OHMTX) 和肌素.
评估单个和组合生物标志物的预测性能,以在儿科ALL患者中延迟MTX消除.
为了能够及早识别延迟消除,以便及时进行治疗干预.

主要方法:

血清样本使用蛋白质沉进行处理.
在Agilent Poroshell 120 SB-C18柱上分离了分析物,其中有甲醇/酸梯度.
使用LC-MS/MS进行量化,通过接收器操作特征 (ROC) 分析评估预测性性能.

主要成果:

LC-MS/MS测定证明了MTX,7-OHMTMTX和肌素的优良线性,准确性和精度.
48小时 (MTX48h) 血清MTX水平显示出与7-OHMTX48h (AUC=0.683) 相比,延迟排泄的预测精度 (AUC=0.914) 更高.
对MTX48h,7-OHMTX48h,7-OHMTX/MTX比率和肌素48h的综合分析实现了最高的预测准确度 (AUC=0.963),识别了较早的延迟排泄 (48h vs 72h).

结论:

开发的LC-MS/MS方法为监测儿科ALL的HDMTX治疗提供了一个强大而可靠的工具.
血清MTX48h是延迟消除的强有力的预测因素,而四种生物标志物的组合提供了卓越的预测能力.
早期检测延迟的MTX消除允许迅速调整酸救援,可能提高治疗效率和安全性.

关键词:

7-氧甲三甲酸 7-氧甲三甲酸液体染色学-并联质谱学质谱学甲基甲酸二醇的使用方法血清中的肌氨酸.治疗药物监测治疗药物监测

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