Startseite Development and validation of a novel 7α-hydroxy-4-cholesten-3-one (C4) liquid chromatography tandem mass spectrometry method and its utility to assess pre-analytical stability
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Development and validation of a novel 7α-hydroxy-4-cholesten-3-one (C4) liquid chromatography tandem mass spectrometry method and its utility to assess pre-analytical stability

  • Jonathan S. Atkins ORCID logo EMAIL logo , Brian G. Keevil , Angela E. Taylor , Christian Ludwig und James M. Hawley
Veröffentlicht/Copyright: 5. August 2024
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Clinical Chemistry and Laboratory Medicine (CCLM)
Aus der Zeitschrift Clinical Chemistry and Laboratory Medicine (CCLM) Band 63 Heft 1

Abstract

Objectives

7α-Hydroxy-4-cholesten-3-one (C4) is the common intermediary of both primary bile acids. C4 is recommended by the British Society of Gastroenterology for the investigation of bile acid diarrhoea (BAD) in patients with chronic diarrhoea. This project aimed to develop and validate an assay to quantitate C4 in serum and assess the stability of C4 in unseparated blood.

Methods

Accuracy was underpinned by calibrating to quantitative nuclear magnetic resonance analysis. C4 was analysed in a 96-well plate format with a deuterated C4 internal standard and liquid-liquid extraction. Validation followed the 2018 Food and Drug Administration guidelines. To assess C4 stability, healthy volunteers (n=12) donated 8 fasted samples each. Samples were incubated at 20 °C for up to 72 h and retrieved, centrifuged, aliquoted and frozen for storage at different time points prior to C4 analysis.

Results

The C4 method demonstrated excellent analytical performance and passed all validation criteria. The method was found to be accurate, precise, free from matrix effects and interference. After 72 h of delayed sample separation, C4 concentration gradually declined by up to 14 % from baseline. However, the change was not significant for up to 12 h.

Conclusions

We present a robust method of analysing serum C4, offering a convenient alternative to 75SeHCAT for BAD investigation. C4 was found to decline in unseparated blood over time; however, after 12 h the mean change was <5 % from baseline. Our results suggest C4 is suitable for collection from both primary and secondary care prior to gastroenterology referral.

Keywords: LC-MS/MS; 7α-hydroxy-4-cholesten-3-one; bile acid diarrhoea; C4; SeHCAT; bile acid malabsorption
Corresponding author: Jonathan S. Atkins, Department of Clinical Biochemistry, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Southmoor Road, Wythenshawe, UK, E-mail:

  1. Research ethics: Sample collection and handling was ethically approved by Health and Care Research Wales on behalf of Manchester University NHS Foundation Trust (IRAS project ID: 273368, Local MFT ID: B00914). The study was conducted in accordance with the Declaration of Helinski (as revised in 2013).

  2. Informed consent: Informed consent was obtained from all individuals included in this study, or their legal guardians or wards.

  3. Author contributions: The authors have accepted responsibility for the entire content of this manuscript and approved its submission. BGK and JMH conceived of the study. JSA and JMH completed the development and validation work. CL performed the quantitative nuclear magnetic resonance spectroscopy. JSA performed the stability study and prepared the first draft of the manuscript. All authors reviewed and edited the manuscript and approved the final draft.

  4. Competing interests: The authors state no competing interests.

  5. Research funding: None declared.

  6. Data availability: The raw data can be obtained on request from the corresponding author.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/cclm-2024-0275).

Received: 2024-02-29
Accepted: 2024-07-12
Published Online: 2024-08-05
Published in Print: 2025-01-29

© 2024 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. Blood self-sampling: friend or foe?
  4. Reviews
  5. Blood self-sampling devices: innovation, interpretation and implementation in total lab automation
  6. Salivary fatty acids in humans: a comprehensive literature review
  7. Opinion Papers
  8. EFLM Task Force Preparation of Labs for Emergencies (TF-PLE) recommendations for reinforcing cyber-security and managing cyber-attacks in medical laboratories
  9. Point-of-care testing: state-of-the art and perspectives
  10. A standard to report biological variation data studies – based on an expert opinion
  11. Ethical Checklists for Clinical Research Projects and Laboratory Medicine: two tools to evaluate compliance with bioethical principles in different settings
  12. Guidelines and Recommendations
  13. Assessment of cardiovascular risk and physical activity: the role of cardiac-specific biomarkers in the general population and athletes
  14. Genetics and Molecular Diagnostics
  15. Clinical utility of regions of homozygosity (ROH) identified in exome sequencing: when to pursue confirmatory uniparental disomy testing for imprinting disorders?
  16. An ultrasensitive DNA-enhanced amplification method for detecting cfDNA drug-resistant mutations in non-small cell lung cancer with selective FEN-assisted degradation of dominant somatic fragments
  17. General Clinical Chemistry and Laboratory Medicine
  18. The biological variation of insulin resistance markers: data from the European Biological Variation Study (EuBIVAS)
  19. The surveys on quality indicators for the total testing process in clinical laboratories of Fujian Province in China from 2018 to 2023
  20. Preservation of urine specimens for metabolic evaluation of recurrent urinary stone formers
  21. Performance evaluation of a smartphone-based home test for fecal calprotection
  22. Implications of monoclonal gammopathy and isoelectric focusing pattern 5 on the free light chain kappa diagnostics in cerebrospinal fluid
  23. Development and validation of a novel 7α-hydroxy-4-cholesten-3-one (C4) liquid chromatography tandem mass spectrometry method and its utility to assess pre-analytical stability
  24. Establishment of ELISA-comparable moderate and high thresholds for anticardiolipin and anti-β2 glycoprotein I chemiluminescent immunoassays according to the 2023 ACR/EULAR APS classification criteria and evaluation of their diagnostic performance
  25. Reference Values and Biological Variations
  26. Capillary blood parameters are gestational age, birthweight, delivery mode and gender dependent in healthy preterm and term infants
  27. Reference intervals and percentiles for soluble transferrin receptor and sTfR/log ferritin index in healthy children and adolescents
  28. Cancer Diagnostics
  29. Detection of serum CC16 by a rapid and ultrasensitive magnetic chemiluminescence immunoassay for lung disease diagnosis
  30. Cardiovascular Diseases
  31. The role of functional vitamin D deficiency and low vitamin D reservoirs in relation to cardiovascular health and mortality
  32. Annual Reviewer Acknowledgment
  33. Reviewer Acknowledgment
  34. Letters to the Editor
  35. EFLM Task Force Preparation of Labs for Emergencies (TF-PLE) survey on cybersecurity
  36. Comment on Lippi et al.: EFLM Task Force Preparation of Labs for Emergencies (TF-PLE) recommendations for reinforcing cyber-security and managing cyber-attacks in medical laboratories
  37. Six Sigma in laboratory medicine: the unfinished symphony
  38. Navigating complexities in vitamin D and cardiovascular health: a call for comprehensive analysis
  39. Simplified preanalytical laboratory procedures for therapeutic drug monitoring (TDM) in patients treated with high-dose methotrexate (HD-MTX) and glucarpidase
  40. New generation of Abbott enzyme assays: imprecision, methods comparison, and impact on patients’ results
  41. Correction of negative-interference from calcium dobesilate in the Roche sarcosine oxidase creatinine assay using CuO
  42. Two cases of MTHFR C677T polymorphism typing failure by Taqman system due to MTHFR 679 GA heterozygous mutation
  43. A falsely elevated blood alcohol concentration (BAC) related to an intravenous administration of phenytoin sodium
https://doi.org/10.1515/cclm-2024-0275
Schlagwörter für diesen Artikel
LC-MS/MS; 7α-hydroxy-4-cholesten-3-one; bile acid diarrhoea; C4; SeHCAT; bile acid malabsorption

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. Blood self-sampling: friend or foe?
  4. Reviews
  5. Blood self-sampling devices: innovation, interpretation and implementation in total lab automation
  6. Salivary fatty acids in humans: a comprehensive literature review
  7. Opinion Papers
  8. EFLM Task Force Preparation of Labs for Emergencies (TF-PLE) recommendations for reinforcing cyber-security and managing cyber-attacks in medical laboratories
  9. Point-of-care testing: state-of-the art and perspectives
  10. A standard to report biological variation data studies – based on an expert opinion
  11. Ethical Checklists for Clinical Research Projects and Laboratory Medicine: two tools to evaluate compliance with bioethical principles in different settings
  12. Guidelines and Recommendations
  13. Assessment of cardiovascular risk and physical activity: the role of cardiac-specific biomarkers in the general population and athletes
  14. Genetics and Molecular Diagnostics
  15. Clinical utility of regions of homozygosity (ROH) identified in exome sequencing: when to pursue confirmatory uniparental disomy testing for imprinting disorders?
  16. An ultrasensitive DNA-enhanced amplification method for detecting cfDNA drug-resistant mutations in non-small cell lung cancer with selective FEN-assisted degradation of dominant somatic fragments
  17. General Clinical Chemistry and Laboratory Medicine
  18. The biological variation of insulin resistance markers: data from the European Biological Variation Study (EuBIVAS)
  19. The surveys on quality indicators for the total testing process in clinical laboratories of Fujian Province in China from 2018 to 2023
  20. Preservation of urine specimens for metabolic evaluation of recurrent urinary stone formers
  21. Performance evaluation of a smartphone-based home test for fecal calprotection
  22. Implications of monoclonal gammopathy and isoelectric focusing pattern 5 on the free light chain kappa diagnostics in cerebrospinal fluid
  23. Development and validation of a novel 7α-hydroxy-4-cholesten-3-one (C4) liquid chromatography tandem mass spectrometry method and its utility to assess pre-analytical stability
  24. Establishment of ELISA-comparable moderate and high thresholds for anticardiolipin and anti-β2 glycoprotein I chemiluminescent immunoassays according to the 2023 ACR/EULAR APS classification criteria and evaluation of their diagnostic performance
  25. Reference Values and Biological Variations
  26. Capillary blood parameters are gestational age, birthweight, delivery mode and gender dependent in healthy preterm and term infants
  27. Reference intervals and percentiles for soluble transferrin receptor and sTfR/log ferritin index in healthy children and adolescents
  28. Cancer Diagnostics
  29. Detection of serum CC16 by a rapid and ultrasensitive magnetic chemiluminescence immunoassay for lung disease diagnosis
  30. Cardiovascular Diseases
  31. The role of functional vitamin D deficiency and low vitamin D reservoirs in relation to cardiovascular health and mortality
  32. Annual Reviewer Acknowledgment
  33. Reviewer Acknowledgment
  34. Letters to the Editor
  35. EFLM Task Force Preparation of Labs for Emergencies (TF-PLE) survey on cybersecurity
  36. Comment on Lippi et al.: EFLM Task Force Preparation of Labs for Emergencies (TF-PLE) recommendations for reinforcing cyber-security and managing cyber-attacks in medical laboratories
  37. Six Sigma in laboratory medicine: the unfinished symphony
  38. Navigating complexities in vitamin D and cardiovascular health: a call for comprehensive analysis
  39. Simplified preanalytical laboratory procedures for therapeutic drug monitoring (TDM) in patients treated with high-dose methotrexate (HD-MTX) and glucarpidase
  40. New generation of Abbott enzyme assays: imprecision, methods comparison, and impact on patients’ results
  41. Correction of negative-interference from calcium dobesilate in the Roche sarcosine oxidase creatinine assay using CuO
  42. Two cases of MTHFR C677T polymorphism typing failure by Taqman system due to MTHFR 679 GA heterozygous mutation
  43. A falsely elevated blood alcohol concentration (BAC) related to an intravenous administration of phenytoin sodium
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