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Mass spectrometry based analytical quality assessment of serum and plasma specimens with patterns of endo- and exogenous peptides

  • Peter Findeisen EMAIL logo , Shruthi Hemanna , Romi Singh Maharjan , Sonani Mindt , Victor Costina , Ralf Hofheinz and Michael Neumaier
Published/Copyright: December 4, 2018
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 57 Issue 5

Abstract

Background

Inappropriate preanalytical sample handling is a major threat for any biomarker discovery approach. Blood specimens have a genuine proteolytic activity that leads to a time dependent decay of peptidic quality control markers (QCMs). The aim of this study was to identify QCMs for direct assessment of sample quality (DASQ) of serum and plasma specimens.

Methods

Serum and plasma specimens of healthy volunteers and tumor patients were spiked with two synthetic reporter peptides (exogenous QCMs) and aged under controlled conditions for up to 24 h. The proteolytic fragments of endogenous and exogenous QCMs were monitored for each time point by mass spectrometry (MS). The decay pattern of peptides was used for supervised classification of samples according to their respective preanalytical quality.

Results

The classification accuracy for fresh specimens (1 h) was 96% and 99% for serum and plasma specimens, respectively, when endo- and exogenous QCMs were used for the calculations. However, classification of older specimens was more difficult and overall classification accuracy decreased to 79%.

Conclusions

MALDI-TOF MS is a simple and robust method that can be used for DASQ of serum and plasma specimens in a high throughput manner. We propose DASQ as a fast and simple step that can be included in multicentric large-scale projects to ensure the homogeneity of sample quality.

Keywords: biobank; biomarker discovery; direct assessment of sample quality; MALDI-TOF mass spectrometry; plasma; preanalytic error; serum
Corresponding author: Prof. Dr. Peter Findeisen, Institute for Clinical Chemistry, Mannheim Medical Faculty of Heidelberg University, University Hospital Mannheim, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany, Phone: +49 621 383 2222, Fax: +49 621 383 3432

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: This work was supported by the grant 01EK1505A from the German Federal Ministry of Education and Research.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Received: 2018-07-30
Accepted: 2018-11-05
Published Online: 2018-12-04
Published in Print: 2019-04-24

©2019 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2018-0811
Keywords for this article
biobank; biomarker discovery; direct assessment of sample quality; MALDI-TOF mass spectrometry; plasma; preanalytic error; serum

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Cardiac biomarkers – 2019
  4. Reviews
  5. Current understanding and future directions in the application of TIMP-2 and IGFBP7 in AKI clinical practice
  6. Serum cytokines, adipokines and ferritin for non-invasive assessment of liver fibrosis in chronic liver disease: a systematic review
  7. Opinion Papers
  8. Detection capability of quantitative faecal immunochemical tests for haemoglobin (FIT) and reporting of low faecal haemoglobin concentrations
  9. Should phosphatidylethanol be currently analysed using whole blood, dried blood spots or both?
  10. IFCC Papers
  11. High sensitivity, contemporary and point-of-care cardiac troponin assays: educational aids developed by the IFCC Committee on Clinical Application of Cardiac Bio-Markers
  12. Cardiac troponin and natriuretic peptide analytical interferences from hemolysis and biotin: educational aids from the IFCC Committee on Cardiac Biomarkers (IFCC C-CB)
  13. Genetics and Molecular Diagnostics
  14. Droplet digital PCR for the simultaneous analysis of minimal residual disease and hematopoietic chimerism after allogeneic cell transplantation
  15. General Clinical Chemistry and Laboratory Medicine
  16. Commutable whole blood reference materials for hemoglobin A1c validated on multiple clinical analyzers
  17. When results matter: reliable creatinine concentrations in hyperbilirubinemia patients
  18. Mass spectrometry based analytical quality assessment of serum and plasma specimens with patterns of endo- and exogenous peptides
  19. Association of serum sphingomyelin profile with clinical outcomes in patients with lower respiratory tract infections: results of an observational, prospective 6-year follow-up study
  20. Effect of an activated charcoal product (DOAC Stop™) intended for extracting DOACs on various other APTT-prolonging anticoagulants
  21. Hematology and Coagulation
  22. Commutability assessment of reference materials for the enumeration of lymphocyte subsets
  23. Circulating platelet-neutrophil aggregates as risk factor for deep venous thrombosis
  24. Reference Values and Biological Variations
  25. A comparison of complete blood count reference intervals in healthy elderly vs. younger Korean adults: a large population study
  26. Indirect determination of hematology reference intervals in adult patients on Beckman Coulter UniCell DxH 800 and Abbott CELL-DYN Sapphire devices
  27. Cancer Diagnostics
  28. Large platelet size is associated with poor outcome in patients with metastatic pancreatic cancer
  29. Cardiovascular Diseases
  30. Sample matrix and high-sensitivity cardiac troponin I assays
  31. Preoperative proteinuria and clinical outcomes in type B aortic dissection after thoracic endovascular aortic repair
  32. Infectious Diseases
  33. The rational specimen for the quantitative detection of Epstein-Barr virus DNA load
  34. Letters to the Editor
  35. Letter to the Editor on article Dimech W, Karakaltsas M, Vincini G. Comparison of four methods of establishing control limits for monitoring quality controls in infectious disease serology testing. Clin Chem Lab Med 2018;56:1970–8
  36. Counterpoint to the Letter to the Editor by Badrick and Parvin in regard to Comparison of four methods of establishing control limits for monitoring quality controls in infectious disease serology testing
  37. Is creatine kinase an ideal biomarker in rhabdomyolysis? Reply to Lippi et al.: Diagnostic biomarkers of muscle injury and exertional rhabdomyolysis (https://doi.org/10.1515/cclm-2018-0656)
  38. Blood neuron cell-derived microparticles as potential biomarkers in Alzheimer’s disease
  39. A fast, nondestructive, low-cost method for the determination of hematocrit of dried blood spots using image analysis
  40. Association of fibroblast growth factor 21 plasma levels with neonatal sepsis: preliminary results
  41. Impact of continuous renal replacement therapy (CRRT) and other extracorporeal support techniques on procalcitonin guided antibiotic therapy in critically ill patients with septic shock
  42. Determining the cutoff value of the APTT mixing test for factor VIII inhibitor
  43. Determining the cut-off value of the APTT mixing test for factor VIII inhibitor: reply
  44. Euthyroid Graves’ disease with spurious hyperthyroidism: a diagnostic challenge
  45. A pilot plasma-ctDNA ring trial for the Cobas® EGFR Mutation Test in clinical diagnostic laboratories
  46. MS-based proteomics: a metrological sound and robust alternative for apolipoprotein E phenotyping in a multiplexed test
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