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一种用于检测汗液和唾液中低浓度肌酐的新型液相色谱-串联质谱分析法,以验证用于连续监测肾功能的生物传感器。

A novel LC-MS/MS assay for low concentrations of creatinine in sweat and saliva to validate biosensors for continuous monitoring of renal function.

作者信息

Adelaars Sophie, Lapré Chyara S M, Raaijmakers Patricia, Konings Constantijn J A M, Mischi Massimo, Bouwman R Arthur, van de Kerkhof Daan

机构信息

Department of Electrical Engineering, Signal Processing Systems, Eindhoven University of Technology, Eindhoven 5612 AE, The Netherlands; Department of Anesthesiology, Catharina Hospital Eindhoven, Eindhoven 5623 EJ, The Netherlands; Clinical Laboratory, Catharina Hospital Eindhoven, Eindhoven 5623 EJ, The Netherlands.

Clinical Laboratory, Catharina Hospital Eindhoven, Eindhoven 5623 EJ, The Netherlands.

出版信息

J Chromatogr B Analyt Technol Biomed Life Sci. 2025 Feb 1;1252:124444. doi: 10.1016/j.jchromb.2024.124444. Epub 2024 Dec 30.

DOI:10.1016/j.jchromb.2024.124444
PMID:39761609
Abstract

Monitoring of kidney function traditionally relies on plasma creatinine concentrations, necessitating invasive blood draws. Non-invasively obtainable biofluids, such as sweat and saliva, present a patient-friendly alternative with potential for continuous monitoring. This study focusses on developing and validating a novel Liquid Chromatography- tandem Mass Spectrometry (LC-MS/MS) assay as a reference test for measuring low creatinine concentrations in sweat and saliva. We explore the correlation between these biofluids and plasma creatinine concentrations during haemodialysis to support future biosensor applications. Creatinine concentrations were measured in sweat, saliva, and plasma obtained from forty patients undergoing haemodialysis. A novel LC-MS/MS assay was developed to quantify low creatinine concentrations in sweat and saliva. Correlation analyses were performed to compare the creatinine concentrations across biofluids. The novel LC-MS assay demonstrated high accuracy (93.9-97.8%) and low imprecision (3.4-8%) in measuring very low creatinine concentrations with a limit of quantitation of 1.26 µmol/L. Significant correlations ware found between creatinine concentrations in sweat and saliva with those in plasma (ρ: 0.68 and 0.80, respectively). During haemodialysis, creatinine concentrations decreased concurrently in all three biofluids. The strong correlations observed imply that these non-invasive biofluids could serve as reliable alternatives to traditional blood tests for kidney function assessment. This study enhances our understanding of creatinine excretion pathways of creatinine and provides a foundation for developing innovative, patient-friendly approaches for continuous kidney function monitoring, such as wearable biosensors.

摘要

传统上,肾功能监测依赖于血浆肌酐浓度,这需要进行侵入性采血。汗液和唾液等可通过非侵入性获取的生物流体提供了一种对患者友好的替代方法,具有连续监测的潜力。本研究专注于开发和验证一种新型液相色谱 - 串联质谱(LC-MS/MS)测定法,作为测量汗液和唾液中低肌酐浓度的参考测试。我们探索了这些生物流体与血液透析期间血浆肌酐浓度之间的相关性,以支持未来生物传感器的应用。对40名接受血液透析的患者的汗液、唾液和血浆中的肌酐浓度进行了测量。开发了一种新型LC-MS/MS测定法来定量汗液和唾液中的低肌酐浓度。进行了相关性分析以比较不同生物流体中的肌酐浓度。这种新型LC-MS测定法在测量极低肌酐浓度时显示出高准确度(93.9 - 97.8%)和低不精密度(3.4 - 8%),定量限为1.26 µmol/L。发现汗液和唾液中的肌酐浓度与血浆中的肌酐浓度之间存在显著相关性(分别为ρ:0.68和0.80)。在血液透析期间,所有三种生物流体中的肌酐浓度同时下降。观察到的强相关性意味着这些非侵入性生物流体可以作为传统血液检测评估肾功能的可靠替代方法。本研究增进了我们对肌酐排泄途径的理解,并为开发创新的、对患者友好的连续肾功能监测方法(如可穿戴生物传感器)奠定了基础。

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