Startseite A novel immunoprecipitation-based targeted liquid chromatography-tandem mass spectrometry analysis for accurate determination for copeptin in human serum
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A novel immunoprecipitation-based targeted liquid chromatography-tandem mass spectrometry analysis for accurate determination for copeptin in human serum

  • Danni Mu , Xiaoli Ma , Yichen Ma , Danchen Wang , Yutong Zou , Ying Zhu , Jian Zhong , Dandan Sun , Yicong Yin , Yumeng Gao , Yuemeng Li , Shi Chen , Huijuan Zhu , Songlin Yu EMAIL logo , Ling Qiu EMAIL logo und Xinqi Cheng ORCID logo EMAIL logo
Veröffentlicht/Copyright: 10. Juli 2025
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Clinical Chemistry and Laboratory Medicine (CCLM)
Aus der Zeitschrift Clinical Chemistry and Laboratory Medicine (CCLM) Band 63 Heft 10

Abstract

Objectives

Copeptin, a stable and simple-to-measure surrogate marker for arginine vasopressin (AVP), demonstrates excellent clinical values, particularly in diagnosing polyuria-polydipsia syndromes. However, conventional immunoassay methods are limited and lack comparability. Our aim was to establish a targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantifying copeptin in human serum.

Methods

Copeptin was extracted from serum using immunoprecipitation, digested with trypsin, and prepared using anion exchange solid-phase extraction before LC-MS/MS detection. The analytical performance was validated in accordance with current guidelines. The method was compared to an immunofluorescent assay on the B.R.A.H.M.S platform.

Results

The LC-MS/MS method had a runtime of 8.5 min. The within-run precision ranged from 5.2 to 12.1 %, and total coefficients of variation ranged from 8.1 to 13.5 %. Copeptin quantitation showed linearity within the range of 5–1,000 pg/mL, with a limit of detection of 2.5 pg/mL. Recovery rates ranged from 95.2 to 103.1 %, and no significant matrix effect was observed with internal standard correction. The LC-MS/MS method had a good consistency with the immunoassay (r=0.926, slope=0.989). The reference interval for healthy individuals was 3.66–58.25 pg/mL.

Conclusions

We demonstrated the accuracy and reliability of this targeted LC-MS/MS method for quantifying copeptin. This innovative application showed satisfactory precision, a wide linear range, and a low limit of detection. Clinical studies are anticipated to be conducted to assess diagnostic accuracy using this method.

Keywords: biomarker; copeptin; immunoprecipitation; liquid chromatography-tandem mass spectrometry; quantitation
Corresponding author: Songlin Yu, Department of Laboratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, No. 1 Shuaifu Yuan, Dongcheng District, Beijing, 100730, P.R. China, E-mail: ; and Ling Qiu, Department of Laboratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, No. 1 Shuaifu Yuan, Dongcheng District, Beijing, 100730, China; and State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China, E-mail: ; and Xinqi Cheng, Department of Laboratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, No. 1 Shuaifu Yuan, Dongcheng District, Beijing, 100730, P.R. China, E-mail:

Funding source: Noncommunicable Chronic Diseases-National Science and Technology Major Project

Award Identifier / Grant number: 2024ZD0533200

Funding source: National Key Technologies R&D Program provided by Ministry of Science and Technology of the People’s Republic of China

Award Identifier / Grant number: 2022YFC3602300/2022YFC3602302

Funding source: National High Level Hospital Clinical Research Funding

Award Identifier / Grant number: 2022-PUMCH-B-073

  1. Research ethics: All procedures performed in studies involving human participants were in accordance with the ethical standards of the Ethics Committee of Peking Union Medical College & Chinese Academy of Medical Sciences, Peking Union Medical College Hospital (ethical approval document number: K-3634) and were in accordance with the Declaration of Helsinki.

  2. Informed consent: Informed consent was exempted by the Ethics Committee of Peking Union Medical College & Chinese Academy of Medical Sciences, Peking Union Medical College Hospital.

  3. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission. Mu: Methodology, Formal analysis, and Writing - Original Draft. X. Ma, Y. Ma, Y. Zou: Investigation. D. Wang, S. Yu, and Y. Zhu: Resources. J. Zhong, D. Sun, Y. Yin: Data Curation. Y. Gao and Y. Li: Visualization. S. Chen and H. Zhu: Conceptualization. S. Yu: Conceptualization, Supervision, Funding acquisition. L. Qiu: Supervision, Funding acquisition. X. Cheng: Supervision, Funding acquisition, Project administration, Writing - Review & Editing.

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

  5. Conflict of interest: The authors state no conflict of interest.

  6. Research funding: This research was funded by the Noncommunicable Chronic Diseases-National Science and Technology Major Project (2024ZD0533200), the National Key Technologies R&D Program provided by Ministry of Science and Technology of the People’s Republic of China (2022YFC3602300/2022YFC3602302), and the National High Level Hospital Clinical Research Funding (2022-PUMCH-B-073).

  7. Data availability: Not applicable.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/cclm-2025-0022).

Received: 2025-01-08
Accepted: 2025-05-04
Published Online: 2025-07-10
Published in Print: 2025-09-25

© 2025 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2025-0022
Schlagwörter für diesen Artikel
biomarker; copeptin; immunoprecipitation; liquid chromatography-tandem mass spectrometry; quantitation

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. Quality indicators: an evolving target for laboratory medicine
  4. Reviews
  5. Regulating the future of laboratory medicine: European regulatory landscape of AI-driven medical device software in laboratory medicine
  6. The spectrum of nuclear patterns with stained metaphase chromosome plate: morphology nuances, immunological associations, and clinical relevance
  7. Opinion Papers
  8. Comprehensive assessment of medical laboratory performance: a 4D model of quality, economics, velocity, and productivity indicators
  9. Detecting cardiac injury: the next generation of high-sensitivity cardiac troponins improving diagnostic outcomes
  10. Perspectives
  11. Can Theranos resurrect from its ashes?
  12. Guidelines and Recommendations
  13. Australasian guideline for the performance of sweat chloride testing 3rd edition: to support cystic fibrosis screening, diagnosis and monitoring
  14. General Clinical Chemistry and Laboratory Medicine
  15. Recommendations for the integration of standardized quality indicators for glucose point-of-care testing
  16. A cost-effective assessment for the combination of indirect immunofluorescence and solid-phase assay in ANA-screening
  17. Assessment of measurement uncertainty of immunoassays and LC-MS/MS methods for serum 25-hydroxyvitamin D
  18. A novel immunoprecipitation-based targeted liquid chromatography-tandem mass spectrometry analysis for accurate determination for copeptin in human serum
  19. Histamine metabolite to basal serum tryptase ratios in systemic mastocytosis and hereditary alpha tryptasemia using a validated LC-MS/MS approach
  20. Machine learning algorithms with body fluid parameters: an interpretable framework for malignant cell screening in cerebrospinal fluid
  21. Impact of analytical bias on machine learning models for sepsis prediction using laboratory data
  22. Immunochemical measurement of urinary free light chains and Bence Jones proteinuria
  23. Serum biomarkers as early indicators of outcomes in spontaneous subarachnoid hemorrhage
  24. High myoglobin plasma samples risk being reported as falsely low due to antigen excess – follow up after a 2-year period of using a mitigating procedure
  25. Candidate Reference Measurement Procedures and Materials
  26. Commutability evaluation of glycated albumin candidate EQA materials
  27. Reference Values and Biological Variations
  28. Health-related reference intervals for heavy metals in non-exposed young adults
  29. Hematology and Coagulation
  30. Practical handling of hemolytic, icteric and lipemic samples for coagulation testing in European laboratories. A collaborative survey from the European Organisation for External Quality Assurance Providers in Laboratory Medicine (EQALM)
  31. Cancer Diagnostics
  32. Assessment of atypical cells in detecting bladder cancer in female patients
  33. Cardiovascular Diseases
  34. False-positive cardiac troponin I values due to macrotroponin in healthy athletes after COVID-19
  35. Diabetes
  36. A comparison of current methods to measure antibodies in type 1 diabetes
  37. Letters to the Editor
  38. The neglected issue of pyridoxal- 5′ phosphate
  39. Error in prostate-specific antigen levels after prostate cancer treatment with radical prostatectomy
  40. Arivale is dead ‒ Hooke is alive
  41. A single dose of 20-mg of ostarine is detectable in hair
  42. Growing importance of vocabularies in medical laboratories
  43. Congress Abstracts
  44. 62nd National Congress of the Hungarian Society of Laboratory Medicine Szeged, Hungary, August 28–30, 2025
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