Reproducibility Evaluation of Urinary Peptide Detection Using CE-MS

Molecules, vol. 26, pp. 7260

Abstract

In recent years, capillary electrophoresis coupled to mass spectrometry (CE-MS) has been increasingly applied in clinical research especially in the context of chronic and age-associated diseases, such as chronic kidney disease, heart failure and cancer. Biomarkers identified using this technique are already used for diagnosis, prognosis and monitoring of these complex diseases, as well as patient stratification in clinical trials. CE-MS allows for a comprehensive assessment of small molecular weight proteins and peptides (<20 kDa) through the combination of the high resolution and reproducibility of CE and the distinct sensitivity of MS, in a high-throughput system. In this study we assessed CE-MS analytical performance with regards to its inter- and intra-day reproducibility, variability and efficiency in peptide detection, along with a characterization of the urinary peptidome content. To this end, CE-MS performance was evaluated based on 72 measurements of a standard urine sample (60 for inter- and 12 for intra-day assessment) analyzed during the second quarter of 2021. Analysis was performed per run, per peptide, as well as at the level of biomarker panels. The obtained datasets showed high correlation between the different runs, low variation of the ten highest average individual log2 signal intensities (coefficient of variation, CV < 10%) and very low variation of biomarker panels applied (CV close to 1%). The findings of the study support the analytical performance of CE-MS, underlining its value for clinical application.

Authors 6

1. Emmanouil Mavrogeorgis Aachen Institute for Molecular Cardiovascular Research

   Universitätsklinikum Aachen · Mosaiques Diagnostics and Therapeutics (Germany) · RWTH Aachen University

   Affiliation as printed

   Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University Hospital, 52074 Aachen, Germany

   Mosaiques Diagnostics GmbH, 30659 Hannover, Germany

2. Harald Mischak

   Mosaiques Diagnostics and Therapeutics (Germany)

   Affiliation as printed

   Mosaiques Diagnostics GmbH, 30659 Hannover, Germany

3. Agnieszka Latosińska

   Mosaiques Diagnostics and Therapeutics (Germany)

   Affiliation as printed

   Mosaiques Diagnostics GmbH, 30659 Hannover, Germany

4. Justyna Siwy

   Mosaiques Diagnostics and Therapeutics (Germany)

   Affiliation as printed

   Mosaiques Diagnostics GmbH, 30659 Hannover, Germany

5. Vera Jankowski Aachen Institute for Molecular Cardiovascular Research

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University Hospital, 52074 Aachen, Germany

6. Joachim Jankowski corresponding Aachen Institute for Molecular Cardiovascular Research

   Maastricht University · Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Experimental Vascular Pathology, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, 6229 Maastricht, The Netherlands

   Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University Hospital, 52074 Aachen, Germany