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Comparative evaluation of peptide vs. protein-based calibration for quantification of cardiac troponin I using ID-LC-MS/MS

  • Meltem Asicioglu ORCID logo , Claudia Swart ORCID logo , Evren Saban ORCID logo , Emrah Yurek , Nevin Gul Karaguler ORCID logo and Merve Oztug ORCID logo EMAIL logo
Published/Copyright: January 3, 2025
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 63 Issue 5

Abstract

Objectives

An analytical protocol based on isotope dilution liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS), which includes a peptide-based calibration strategy, was developed and validated for the determination of cardiac troponin I (cTnI) levels in clinical samples. Additionally, the developed method was compared with a protein-based calibration strategy, using cTnI serving as a model for low-abundant proteins. The aim is to evaluate new approaches for protein quantification in complex matrices, supporting the metrology community in implementing new methods and developing fit-for-purpose SI- traceable peptide or protein primary calibrators.

Methods

To establish traceability to SI units, peptide impurity correction amino acid analysis (PICAA) was conducted to determine the absolute content of signature peptides in the primary standards. Immunoaffinity enrichment was used to capture cTnI from human serum, with a comparison between microbeads and nanobeads to improve enrichment efficiency. Parallel reaction monitoring was used to monitor two signature peptides specific to cTnI. Various digestion parameters were optimized to achieve complete digestion.

Results

The analytical method demonstrated selectivity and specificity, allowing the quantification of cTnI within 0.9–22.0 μg/L. The intermediate precision RSD was below 28.9 %, and the repeatability RSD was below 5.8 % at all concentration levels, with recovery rates ranging from 87 % to 121 %. The comparison of calibration strategies showed similar LOQ values, but the peptide-based calibration exhibited significant quantitative bias in recovery rates. The data are available via ProteomeXchange (PXD055104).

Conclusions

This isotope dilution liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) method, based on peptide calibration, successfully quantified cTnI in human serum. Comparing this with protein-based calibration highlighted both the strengths and potential limitations of peptide-based strategies.

Keywords: peptide impurity correction amino acid analysis (PICAA); isotope dilution mass spectrometry (ID-MS); cTnI; peptide-based calibration; magnetic particles; immunoaffinity enrichment
Corresponding author: Dr. Merve Oztug, PhD, TÜBİTAK Gebze Yerleskesi, UME, TÜBİTAK National Metrology Institute (TÜBİTAK UME), 41400 Gebze, Kocaeli, Türkiye; Department of Molecular Biology and Genetics, Faculty of Science and Letters, Istanbul Technical University, Istanbul, Türkiye; and Dr. Orhan Ocalgiray Molecular Biology-Biotechnology and Genetics Research Center, Istanbul Technical University, Istanbul, Türkiye, E-mail:

Funding source: European Metrology Programme for Innovation and Research

Award Identifier / Grant number: 18HLT10 CardioMet

Funding source: Istanbul Technical University Scientific Research Projects Coordination Unit (BAP)

Award Identifier / Grant number: 45126

  1. Research ethics: All individuals who provided blood samples were enrolled into the study in full accordance with the guidelines approved and monitored by the Ethics Committee of the Acibadem University in Istanbul. All procedures were in accordance with the Helsinki Declaration. All samples used were exclusively anonymized leftover samples.

  2. Informed consent: Not applicable.

  3. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission. Meltem Asicioglu: conceptualization, methodology, validation, investigation, resources, data curation, writing – original draft, visualization. Claudia Swart: conceptualization, methodology, review & editing. Evren Saban: methodology. Emrah Yurek: procurement of clinical samples, ethical permission. Nevin Gul Karaguler: review & editing, supervision. Merve Oztug: conceptualization, methodology, data curation, review & editing, supervision.

  4. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  5. Conflict of interest: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

  6. Research funding: This project was supported by EMPIR programme co-financed by Participating States and from the European Union’s Horizon 2020 research and innovation programme for supporting this project under 18HLT10 CardioMet and Istanbul Technical University Scientific Research Projects Coordination Unit (BAP) for supporting this project numbered 45126.

  7. Data availability: The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE [24] partner repository with the dataset identifier PXD055104.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/cclm-2024-0999).

Received: 2024-08-27
Accepted: 2024-12-16
Published Online: 2025-01-03
Published in Print: 2025-04-28

© 2024 Walter de Gruyter GmbH, Berlin/Boston

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  2. Editorial
  3. Are the benefits of External Quality Assessment (EQA) recognized beyond the echo chamber?
  4. Reviews
  5. Behind the scenes of EQA – characteristics, capabilities, benefits and assets of external quality assessment (EQA): Part I – EQA in general and EQA programs in particular
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  7. Behind the scenes of EQA – characteristics, capabilities, benefits and assets of external quality assessment (EQA): Part III – EQA samples
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  24. An untargeted metabolomics approach to evaluate enzymatically deconjugated steroids and intact steroid conjugates in urine as diagnostic biomarkers for adrenal tumors
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  26. Comparative evaluation of peptide vs. protein-based calibration for quantification of cardiac troponin I using ID-LC-MS/MS
  27. Infectious Diseases
  28. The potential role of leukocytes cell population data (CPD) for diagnosing sepsis in adult patients admitted to the intensive care unit
  29. Letters to the Editor
  30. Concentrations and agreement over 10 years with different assay versions and analyzers for troponin T and N-terminal pro-B-type natriuretic peptide
  31. Does blood tube filling influence the Athlete Biological Passport variables?
  32. Influence of data visualisations on laboratorians’ acceptance of method comparison studies
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https://doi.org/10.1515/cclm-2024-0999
Keywords for this article
peptide impurity correction amino acid analysis (PICAA); isotope dilution mass spectrometry (ID-MS); cTnI; peptide-based calibration; magnetic particles; immunoaffinity enrichment

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Are the benefits of External Quality Assessment (EQA) recognized beyond the echo chamber?
  4. Reviews
  5. Behind the scenes of EQA – characteristics, capabilities, benefits and assets of external quality assessment (EQA): Part I – EQA in general and EQA programs in particular
  6. Behind the scenes of EQA – characteristics, capabilities, benefits and assets of external quality assessment (EQA): Part II – EQA cycles
  7. Behind the scenes of EQA – characteristics, capabilities, benefits and assets of external quality assessment (EQA): Part III – EQA samples
  8. Behind the scenes of EQA–characteristics, capabilities, benefits and assets of external quality assessment (EQA): Part IV – Benefits for participant laboratories
  9. Behind the scenes of EQA – characteristics, capabilities, benefits and assets of external quality assessment (EQA): Part V – Benefits for stakeholders other than participants
  10. Opinion Papers
  11. Not all biases are created equal: how to deal with bias on laboratory measurements
  12. Krebs von den Lungen-6 (KL-6) as a diagnostic and prognostic biomarker for non-neoplastic lung diseases
  13. General Clinical Chemistry and Laboratory Medicine
  14. Evaluation of performance in preanalytical phase EQA: can laboratories mitigate common pitfalls?
  15. Point-of-care testing improves care timeliness in the emergency department. A multicenter randomized clinical trial (study POCTUR)
  16. The different serum albumin assays influence calcium status in haemodialysis patients: a comparative study against free calcium as a reference method
  17. Measurement of 1,25-dihydroxyvitamin D in serum by LC-MS/MS compared to immunoassay reveals inconsistent agreement in paediatric samples
  18. Knowledge among clinical personnel on the impact of hemolysis using blood gas analyzers
  19. Quality indicators for urine sample contamination: can squamous epithelial cells and bacteria count be used to identify properly collected samples?
  20. Reference Values and Biological Variations
  21. Biological variation of cardiac biomarkers in athletes during an entire sport season
  22. Increased specificity of the “GFAP/UCH-L1” mTBI rule-out test by age dependent cut-offs
  23. Cancer Diagnostics
  24. An untargeted metabolomics approach to evaluate enzymatically deconjugated steroids and intact steroid conjugates in urine as diagnostic biomarkers for adrenal tumors
  25. Cardiovascular Diseases
  26. Comparative evaluation of peptide vs. protein-based calibration for quantification of cardiac troponin I using ID-LC-MS/MS
  27. Infectious Diseases
  28. The potential role of leukocytes cell population data (CPD) for diagnosing sepsis in adult patients admitted to the intensive care unit
  29. Letters to the Editor
  30. Concentrations and agreement over 10 years with different assay versions and analyzers for troponin T and N-terminal pro-B-type natriuretic peptide
  31. Does blood tube filling influence the Athlete Biological Passport variables?
  32. Influence of data visualisations on laboratorians’ acceptance of method comparison studies
  33. An appeal for biological variation estimates in deep immunophenotyping
  34. Serum free light chains reference intervals for the Lebanese population
  35. Applying the likelihood ratio concept in external quality assessment for ANCA
  36. A promising new direct immunoassay for urinary free cortisol determination
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