用于定量检测 COVID-19 患者血浆中尼马瑞韦/利托那韦的简便快速 LC-MS/MS 方法

IF 1.5 4区化学 Q3 CHEMISTRY, ANALYTICAL

International Journal of Analytical Chemistry Pub Date : 2024-03-06 DOI:10.1155/2024/6139928

Xiujing Zhu, Lin Li, Bin Dai, Zhijun Liu, Zhipeng Wang, Lili Cui, Shouhong Gao, Wansheng Chen, Xia Tao, Deduo Xu

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引用次数: 0

摘要

由于潜在的药物相互作用，尼马瑞韦/利托那韦与其他药物的联合处方受到限制，因此治疗药物监测（TDM）变得尤为重要。本研究建立了一种液相色谱-串联质谱（LC-MS/MS）测定COVID-19患者血浆中尼瑞韦酯/利托那韦的方法，为TDM提供了技术和理论支持。血浆样品经乙腈蛋白沉淀处理后，用 Agilent Poroshell 120 SB-C18 (2.1 × 75 mm, 2.7 μm)色谱柱在 35°C 下分离。流动相为乙腈和 0.1%甲酸水溶液（52:48），流速为 0.3 mL/min。在多反应监测（MRM）模式下，使用前体/产物离子监测尼马瑞韦和利托那韦，前体/产物离子分别为 m/z 500.2/110.1 和 721.3/296.1，内标为西利奈德。两种分析物的线性范围为2.0 ng/mL至5000 ng/mL，日间和日内精密度和准确度良好，尼马瑞韦的回收率为92.0%-107%，利托那韦的回收率为85.7%-106%。最后，该方法被成功地应用于监测血液透析患者血浆样本中尼马瑞韦/利托那韦的暴露水平。

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A Simple and Rapid LC-MS/MS Method for the Quantification of Nirmatrelvir/Ritonavir in Plasma of Patients with COVID-19

The combined prescriptions of nirmatrelvir/ritonavir and other drugs are limited due to potential drug-drug interactions, so therapeutic drug monitoring (TDM) becomes particularly important. In this study, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established for determination of the nirmatrelvir/ritonavir in plasma of patients with COVID-19, providing technical and theoretical support for the TDM. Plasma samples were processed by protein precipitation using acetonitrile, and analytes were separated on an Agilent Poroshell 120 SB-C18 (2.1 × 75 mm, 2.7 μm) column at 35°C. Acetonitrile and 0.1% formic acid in water (52 : 48) were utilized as the mobile phases at a flow rate of 0.3 mL/min. In the multiple reaction monitoring (MRM) mode, nirmatrelvir and ritonavir were monitored using precursor/product ions: m/z 500.2/110.1 and 721.3/296.1, respectively, with selinexor as the internal standard. The linear range of both analytes was 2.0 ng/mL to 5000 ng/mL with good inter- and intraday precision and accuracy, and the recovery was 92.0%–107% for nirmatrelvir and 85.7%–106% for ritonavir. Finally, this method was successfully applied to monitor the exposure levels of nirmatrelvir/ritonavir in plasma samples from hemodialysis patients.

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来源期刊

International Journal of Analytical Chemistry CHEMISTRY, ANALYTICAL-

CiteScore

3.10

自引率

5.60%

发文量

117

期刊介绍： International Journal of Analytical Chemistry publishes original research articles that report new experimental results and methods, especially in relation to important analytes, difficult matrices, and topical samples. Investigations may be fundamental, or else related to specific applications; examples being biological, environmental and food testing, and analysis in chemical synthesis and materials processing. As well as original research, the International Journal of Analytical Chemistry also publishes focused review articles that examine the state of the art, identify emerging trends, and suggest future directions for developing fields.