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A quantitative LC-MS/MS method for insulin-like growth factor 1 in human plasma

  • Kees J. Bronsema , Frank Klont , Frank B. Schalk , Rainer Bischoff , Ido P. Kema and Nico C. van de Merbel EMAIL logo
Published/Copyright: May 1, 2018
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 56 Issue 11

Abstract

Background:

Insulin-like growth factor 1 (IGF1) is a biomarker with various applications in medicine and also in doping control.

Methods:

A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed that employs 15N-IGF1 as an internal standard. The method features urea-based IGF1/IGFBP-complex dissociation which is directly followed by tryptic digestion. Following solid-phase extraction (SPE) sample clean-up of the digest, IGF1 is detected by means of two signature peptides that enable quantification of total IGF1 as well as discrimination between IGF1 proteoforms with ‘native’ and modified or extended N-terminal sequences.

Results:

Our method is capable of measuring plasma IGF1 concentrations over the clinically relevant range of 10–1000 ng/mL and was validated according to regulatory guidelines. Comparison with the IDS-iSYS IGF1 immunoassay revealed good correlation (R2>0.97) and no proportional bias between both assays was observed after normalizing the results against the WHO reference standard for IGF1 (02/254). Evaluation of several commercially available IGF1 preparations showed varying responses which were due to inconsistencies in purity and absolute amount of IGF1 present in these products.

Conclusions:

Our LC-MS/MS method introduces urea-based dissociation of IGF1/IGFBP-complexes to enable reliable quantification of IGF1 in plasma. Furthermore, the method is able to detect clinically relevant IGF1 levels without an enrichment procedure at the protein-level and thereby minimizes the risk of losing IGF1 proteoforms during sample preparation.

Keywords: insulin-like growth factor 1 (IGF1); liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS); quantification

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

  2. Research funding: This project was supported by Samenwerkingsverband Noord-Nederland, SNN (grant T3041).

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization 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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Supplementary Material:

The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2017-1042).

Received: 2017-11-09
Accepted: 2018-04-06
Published Online: 2018-05-01
Published in Print: 2018-10-25

©2018 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2017-1042
Keywords for this article
insulin-like growth factor 1 (IGF1); liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS); quantification

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. New biomarkers and traditional cardiovascular risk scores: any crystal ball for current effective advice and future exact prediction?
  4. Reviews
  5. Laboratory sample stability. Is it possible to define a consensus stability function? An example of five blood magnitudes
  6. Updated review of postmortem biochemical exploration of hypothermia with a presentation of standard strategy of sampling and analyses
  7. Long non-coding RNA-mediated regulation of signaling pathways in gastric cancer
  8. Opinion Paper
  9. Long story short: an introduction to the short-term and longterm Six Sigma quality and its importance in laboratory medicine for the management of extra-analytical processes
  10. EFLM Paper
  11. The European Federation of Clinical Chemistry and Laboratory Medicine syllabus for postgraduate education and training for Specialists in Laboratory Medicine: version 5 – 2018
  12. General Clinical Chemistry and Laboratory Medicine
  13. Early availability of laboratory results increases same day ward discharge rates
  14. Evaluation of the clinical implementation of a large-scale online e-learning program on venous blood specimen collection guideline practices
  15. Improved prospective risk analysis for clinical laboratories compensated for the throughput in processes
  16. National surveys on internal quality control for blood gas analysis and related electrolytes in clinical laboratories of China
  17. Clinical validation of S100B in the management of a mild traumatic brain injury: issues from an interventional cohort of 1449 adult patients
  18. A quantitative LC-MS/MS method for insulin-like growth factor 1 in human plasma
  19. Development and validation of a mass spectrometry-based assay for quantification of insulin-like factor 3 in human serum
  20. Anti-ganglioside antibodies: experience from the Italian Association of Neuroimmunology external quality assessment scheme
  21. Reference Values and Biological Variations
  22. Improving IBD diagnosis and monitoring by understanding preanalytical, analytical and biological fecal calprotectin variability
  23. Establishing normal values of total testosterone in adult healthy men by the use of four immunometric methods and liquid chromatography-mass spectrometry
  24. Cancer Diagnostics
  25. Exploring the potential of mucin 13 (MUC13) as a biomarker for carcinomas and other diseases
  26. Cardiovascular Diseases
  27. Prognostic implications of detectable cardiac troponin I below the 99th percentile in patients admitted to an emergency department without acute coronary syndrome
  28. Osteocalcin value to identify subclinical atherosclerosis over atherosclerotic cardiovascular disease (ASCVD) risk score in middle-aged and elderly Chinese asymptomatic men
  29. Infectious Diseases
  30. Comparison of four methods of establishing control limits for monitoring quality controls in infectious disease serology testing
  31. Letter to the Editor
  32. Letter to the Editor relative to Clin Chem Lab Med 2018;56(3):360–372
  33. Update in diagnosis and management of primary aldosteronism: reply to a Letter to the Editor
  34. Can calculated total nitrogen replace Kjeldahl total nitrogen measurements in 24-h urine samples?
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