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

• Published in: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Analytical technologies in the biomedical and life sciences, 2025-02, Vol.1252, p.124444, Article 124444
• Main Authors: Adelaars, Sophie, Lapré, Chyara S.M., Raaijmakers, Patricia, Konings, Constantijn J.A.M., Mischi, Massimo, Bouwman, R. Arthur, van de Kerkhof, Daan
• Format: Article
• Language: English
• Subjects: Adult; Aged; Biosensing Techniques - instrumentation; Biosensing Techniques - methods; Biosensors for sweat analysis; Chromatography, Liquid - methods; Continuous monitoring; Creatinine - analysis; Creatinine - blood; Diagnostics of creatinine in sweat and saliva; Female; Humans; Kidney Function Tests - methods; LC-MS/MS assay development; Limit of Detection; Linear Models; Liquid Chromatography-Mass Spectrometry; Male; Middle Aged; Non-invasive monitoring; Renal Dialysis; Reproducibility of Results; Saliva - chemistry; Sweat - chemistry; Tandem Mass Spectrometry - methods
• ISSN: 1570-0232; 1873-376X; 1873-376X
• DOI: 10.1016/j.jchromb.2024.124444

•A novel LC-MS/MS assay was developed for low creatinine detection in sweat and saliva.•High assay accuracy (93.9–97.8%) and low imprecision (3.4–8.1%) were achieved.•The method serves as a reference standard for validating future wearable biosensors.•Creatinine concentrations in sweat and saliva correlate with plasma during haemodialysis.•Non-invasive biofluids provide a patient-friendly alternative for kidney function monitoring. 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.