Metrological traceability in mass spectrometry-based targeted protein quantitation: A proof-of-principle study for serum apolipoproteins A-I and B100
Abstract
In this study, we have followed up on previous liquid chromatography (LC) multiple reaction monitoring (MRM) mass spectrometry (MS) approaches for measurement of apolipoprotein (apo) A-I and apo B100 in serum aiming for implementation of a multiplexed assay in a clinical chemistry laboratory with full metrological traceability. Signature peptides were selected and detected by dynamic MRM, and stable isotope labeled (SIL)-peptides were used as internal standards. Five apo A-I and four apo B100 peptides were measured in serum digests with linearity (R(2)>0.992) in the physiologically relevant concentration ranges. Linearity with regard to protein concentration was ascertained at five concentration levels (R(2)>0.926 and R(2)>0.965, for the apo A-I and apo B100 peptides, respectively). Three native value-assigned sera were used as external calibrators for further method verification. Imprecision values on sample preparation and LC-MS/MS acquisition were below the established minimal specifications for apo A-I and apo B100 (5.0% and 5.3%, respectively). Correlation of LC-MS/MS results with immunoturbidimetric assay results, for normo- and hypertriglyceridemic samples, showed R(2)>0.944 for apo A-I and R(2)>0.964 for apo B100. This LC-MS/MS method has potential for clinical application in normo- and dyslipidemic patients. Biological significance Measurement of apo A-I and apo B100 may offer an alternative to high and low density lipoprotein cholesterol (HDL-c and LDL-c) methods fo…
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The previously reported manual sample preparation procedure for serum apoA-I and apoB was optimized to improve peptide recoveries and digestion rates for all apolipoproteins.
“Our previously reported manual sample preparation procedure for serum apoA-I and apoB (19, 30, 31) was optimized to improve peptide recoveries and digestion rates for all apolipoproteins (see online Supplemental Data and online Supplemental Fig. 4).”
From Automated multiplex LC-MS/MS assay for quantifying serum apolipoproteins A-I, B, C-I, C-II, C-III, and E with qualitative apolipoprotein E phenotyping (2016) · cites this paper as [19]
Various LC-MS/MS assays for multiplexed quantification of apolipoproteins or phenotyping of apoE have been reported.
“Various LC-MS/MS assays for multiplexed quantification of apolipoproteins (14-23) or phenotyping of apoE (24-27) have been reported.”
From Automated multiplex LC-MS/MS assay for quantifying serum apolipoproteins A-I, B, C-I, C-II, C-III, and E with qualitative apolipoprotein E phenotyping (2016) · cites this paper as [19]
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Self-citationApolipoprotein profiling as a personalized approach to the diagnosis and treatment of dyslipidaemia
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- Authors
- Smit, N. P. M., Romijn, F. P. H. T. M., van den Broek, I., Drijfhout, J. W., Haex, M., van der Laarse, A., van der Burgt, Y. E. M., & Cobbaert, C. M.
- Affiliations
- Leiden University Medical Center (NL)
- Corresponding author
- Smit, Nico P.M.
- ORCID
- Venue
- Journal of Proteomics
- Publisher
- Elsevier BV
- Published
- 2014-09
- Volume
- 109
- Pages
- 143-161
- ISSN
- 1874-3919 (ISSN-L)
- OpenAlex
- W2011267199
- Cited by
- 32
- References
- 4
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2022: 1 · 2021: 4 · 2020: 2 · 2019: 1 · 2018: 4 · 2017: 5 · 2016: 5 · 2015: 5 · 2014: 2
- FWCI
- 2.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Proteomics (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Topics
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Keywords
- apolipoprotein A-I, apolipoprotein B-100, measurement traceability, isotope-labeled internal standards, signature peptides, external calibration, dyslipidemia, cardiovascular disease risk assessment, multiplex assay
- MeSH terms
- Humans, Peptides, Mass Spectrometry, Apolipoprotein A-I, Dyslipidemias, Apolipoprotein B-100
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