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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 and James M. Hawley
Published/Copyright: August 5, 2024
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 63 Issue 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.

References

1. Boyer, JL. Bile formation and secretion. Compr Physiol 2013;3:1035–78. https://doi.org/10.1002/cphy.c120027.Search in Google Scholar PubMed PubMed Central

2. Iqbal, J, Hussain, MM. Intestinal lipid absorption. Am J Physiol Endocrinol Metab 2009;296:E1183–94. https://doi.org/10.1152/ajpendo.90899.2008.Search in Google Scholar PubMed PubMed Central

3. Russell, DW. The enzymes, regulation, and genetics of bile acid synthesis. Annu Rev Biochem 2003;72:137–74. https://doi.org/10.1146/annurev.biochem.72.121801.161712.Search in Google Scholar PubMed

4. Galman, C, Arvidsson, I, Angelin, B, Rudling, M. Monitoring hepatic cholesterol 7 alpha-hydroxylase activity by assay of the stable bile acid intermediate 7 alpha-hydroxy-4-cholesten-3-one in peripheral blood. J Lipid Res 2003;44:859–65.10.1194/jlr.D200043-JLR200Search in Google Scholar PubMed

5. Mottacki, N, Simren, M, Bajor, A. Review article: bile acid diarrhoea – pathogenesis, diagnosis and management. Aliment Pharmacol Ther 2016;43:884–98. https://doi.org/10.1111/apt.13570.Search in Google Scholar PubMed

6. Bajor, A, Kilander, A, Sjovall, H, Rudling, M, Ung, KA. The bile acid turnover rate assessed with the 75SeHCAT test is stable in chronic diarrhoea but slightly decreased in healthy subjects after a long period of time. Dig Dis Sci 2008;53:2935–40. https://doi.org/10.1007/s10620-008-0256-4.Search in Google Scholar PubMed

7. Merrick, MV, Eastwood, MA, Ford, MJ. Is bile-acid malabsorption underdiagnosed – an evaluation of accuracy of diagnosis by measurement by SeHCAT retention. Br Med J 1985;290:665–8. https://doi.org/10.1136/bmj.290.6469.665.Search in Google Scholar PubMed PubMed Central

8. NICE. Diagnostics guidance [DG44]: SeHCAT (tauroselcholic [75 selenium] acid) for diagnosing bile acid diarrhoea. Available from: https://www.nice.org.uk/guidance/dg44/resources [Accessed 14 Aug 2023].Search in Google Scholar

9. Fernandes, DCR, Poon, D, White, LL, Andreyev, HJN. What is the cost of delayed diagnosis of bile acid malabsorption and bile acid diarrhoea? Frontline Gastroenterol 2019;10:72–6. https://doi.org/10.1136/flgastro-2018-101011.Search in Google Scholar PubMed PubMed Central

10. Walters, JRF, Arasaradnam, R, Andreyev, HJN, Network, UKBARD. Diagnosis and management of bile acid diarrhoea: a survey of UK expert opinion and practice. Frontline Gastroenterol 2019;11:358–63. https://doi.org/10.1136/flgastro-2019-101301.Search in Google Scholar PubMed PubMed Central

11. Summers, JA, Peacock, J, Coker, B, McMillan, V, Ofuya, M, Lewis, C, et al.. Multicentre prospective survey of SeHCAT provision and practice in the UK. BMJ Open Gastroenterol 2016;3. https://doi.org/10.1136/bmjgast-2016-000091.Search in Google Scholar PubMed PubMed Central

12. Slattery, SA, Niaz, O, Aziz, Q, Ford, AC, Farmer, AD. Systematic review with meta-analysis: the prevalence of bile acid malabsorption in the irritable bowel syndrome with diarrhoea. Aliment Pharmacol Ther 2015;42:3–11. https://doi.org/10.1111/apt.13227.Search in Google Scholar PubMed

13. Wedlake, L, A’Hern, R, Russell, D, Thomas, K, Walters, JRF, Andreyev, HJN. Systematic review: the prevalence of idiopathic bile acid malabsorption as diagnosed by SeHCAT scanning in patients with diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther 2009;30:707–17. https://doi.org/10.1111/j.1365-2036.2009.04081.x.Search in Google Scholar PubMed

14. Soubieres, A, Wilson, P, Poullis, A, Wilkins, J, Rance, M. Burden of irritable bowel syndrome in an increasingly cost-aware National Health Service. Frontline Gastroenterol 2015;6:246–51. https://doi.org/10.1136/flgastro-2014-100542.Search in Google Scholar PubMed PubMed Central

15. Oka, P, Parr, H, Barberio, B, Black, CJ, Savarino, EV, Ford, AC. Global prevalence of irritable bowel syndrome according to Rome III or IV criteria: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol 2020;5:908–17. https://doi.org/10.1016/s2468-1253(20)30217-x.Search in Google Scholar

16. Eusufzai, S, Axelson, M, Angelin, B, Einarsson, K. Serum 7-alpha-hydroxy-4-cholesten-3-one concentrations in the evaluation of bile-acid malabsorption in patients with diarrhea – correlation to SeHCAT test. Gut 1993;34:698–701. https://doi.org/10.1136/gut.34.5.698.Search in Google Scholar PubMed PubMed Central

17. Brydon, WG, Culbert, P, Kingstone, K, Jarvie, A, Iacucci, M, Tenhage, M, et al.. An evaluation of the use of serum 7-alpha-hydroxycholestenone as a diagnostic test of bile acid malabsorption causing watery diarrhea. Can J Gastroenterol 2011;25:319–23. https://doi.org/10.1155/2011/701287.Search in Google Scholar PubMed PubMed Central

18. Vijayvargiya, P, Camilleri, M, Carlson, P, Lueke, A, O’Neill, J, Burton, D, et al.. Performance characteristics of serum C4 and FGF19 measurements to exclude the diagnosis of bile acid diarrhoea in IBS-diarrhoea and functional diarrhoea. Aliment Pharmacol Ther 2017;46:581–8. https://doi.org/10.1111/apt.14214.Search in Google Scholar PubMed PubMed Central

19. Donato, LJ, Lueke, A, Kenyon, SM, Meeusen, JW, Camilleri, M. Description of analytical method and clinical utility of measuring serum 7-alpha-hydroxy-4-cholesten-3-one (7aC4) by mass spectrometry. Clin Biochem 2018;52:106–11. https://doi.org/10.1016/j.clinbiochem.2017.10.008.Search in Google Scholar PubMed

20. Battat, R, Duijvestein, M, Vande Casteele, N, Singh, S, Dulai, PS, Valasek, MA, et al.. Serum concentrations of 7α-hydroxy-4-cholesten-3-one are associated with bile acid diarrhea in patients with Crohn’s disease. Clin Gastroenterol Hepatol 2019;17:2722–30.e4. https://doi.org/10.1016/j.cgh.2018.11.012.Search in Google Scholar PubMed PubMed Central

21. Borup, C, Wildt, S, Rumessen, J, Graff, J, Bouchelouche, PN, Andersen, TB, et al.. Biochemical diagnosis of bile acid diarrhea: prospective comparison with the (75)seleno-taurohomocholic acid test. Am J Gastroenterol 2020;115:2086–94. https://doi.org/10.14309/ajg.0000000000000772.Search in Google Scholar PubMed

22. Arasaradnam, RP, Brown, S, Forbes, A, Fox, MR, Hungin, P, Kelman, L, et al.. Guidelines for the investigation of chronic diarrhoea in adults: British Society of Gastroenterology. Gut 2018;67:1380–99. https://doi.org/10.1136/gutjnl-2017-315909.Search in Google Scholar PubMed PubMed Central

23. Vasant, DH, Paine, PA, Black, CJ, Houghton, LA, Everitt, HA, Corsetti, M, et al.. British Society of Gastroenterology guidelines on the management of irritable bowel syndrome. Gut 2021;70:1214–40. https://doi.org/10.1136/gutjnl-2021-324598.Search in Google Scholar PubMed

24. US department of Health and Human Services. Food and Drug Administration, Centre for Drug Evaluation and Research (CDER) and Centre for Veterinary Medicine (CVM). Guidance for industry. Bioanalytical method validation. Rockville, MD: FDA; 2018.Search in Google Scholar

25. European Medicines Agency. Guideline on bioanalytical method validation. London, UK: MEA; 2011.Search in Google Scholar

26. Matuszewski, BK, Constanzer, ML, Chavez-Eng, CM. Strategies for the assessment of matrix effect in quantitative bioanalytical methods based on HPLC-MS/MS. Anal Chem 2003;75:3019–30. https://doi.org/10.1021/ac020361s.Search in Google Scholar PubMed

27. Axelson, M, Aly, A, Sjovall, J. Levels of 7-alpha-hydroxy-4-cholesten-3-one in plasma reflect rates of bile-acid synthesis in man. FEBS Lett 1988;239:324–8. https://doi.org/10.1016/0014-5793(88)80944-x.Search in Google Scholar PubMed

28. Yoshida, T, Honda, A, Tanaka, N, Matsuzaki, Y, Shoda, J, He, BF, et al.. Determination of 7-alpha-hydroxy-4-cholesten-3-one level in plasma using isotope-dilution mass-spectrometry and monitoring its circadian-rhythm in human as an index of bile-acid biosynthesis. J Chromatogr B Biomed Appl 1994;655:179–87. https://doi.org/10.1016/0378-4347(94)00107-3.Search in Google Scholar PubMed

29. Brydon, WG, Nyhlin, H, Eastwood, MA, Merrick, MV. Serum 7 alpha-hydroxy-4-cholesten-3-one and selenohomocholyltaurine (SeHCAT) whole body retention in the assessment of bile acid induced diarrhoea. Eur J Gastroenterol Hepatol 1996;8:117–23.10.1097/00042737-199602000-00005Search in Google Scholar PubMed

30. Sauter, GH, Munzing, W, von Ritter, C, Paumgartner, G. Bile acid malabsorption as a cause of chronic diarrhea: diagnostic value of 7alpha-hydroxy-4-cholesten-3-one in serum. Dig Dis Sci 1999;44:14–9. https://doi.org/10.1023/a:1026681512303.10.1016/S0016-5085(98)81677-6Search in Google Scholar

31. Honda, A, Yamashita, K, Numazawa, M, Ikegami, T, Doy, M, Matsuzaki, Y, et al.. Highly sensitive quantification of 7 alpha-hydroxy-4-cholesten-3-one in human serum by LC-ESI-MS/MS. J Lipid Res 2007;48:458–64. https://doi.org/10.1194/jlr.d600032-jlr200.Search in Google Scholar

32. Camilleri, M, Nadeau, A, Tremaine, WJ, Lamsam, J, Burton, D, Odunsi, S, et al.. Measurement of serum 7 alpha-hydroxy-4-cholesten-3-one (or 7 alpha C4), a surrogate test for bile acid malabsorption in health, ileal disease and irritable bowel syndrome using liquid chromatography-tandem mass spectrometry. Neuro Gastroenterol Motil 2009;21:734–E43. https://doi.org/10.1111/j.1365-2982.2009.01288.x.Search in Google Scholar PubMed PubMed Central

33. Yuan, L, Luo, Y, Kandoussi, H, Ji, QC. A simple, fast, sensitive and robust LCMS/MS bioanalytical assay for evaluating 7 alpha-hydroxy-4-cholesten-3-one biomarker in a clinical program. Bioanalysis 2016;8:2445–55. https://doi.org/10.4155/bio-2016-0219.Search in Google Scholar PubMed

34. Kang, LJ, Connolly, TM, Weng, ND, Jian, WY. LC-MS/MS quantification of 7 alpha-hydroxy-4-cholesten-3-one (C4) in rat and monkey plasma. J Chromatogr, B: Anal Technol Biomed Life Sci 2017;1064:49–55. https://doi.org/10.1016/j.jchromb.2017.09.006.Search in Google Scholar PubMed

35. Prost, JC, Brunner, F, Bovet, C, Grob, C, Berchtold, C, Schlotterbeck, G, et al.. A UHPLC-MS/MS method for the quantification of 7 alpha-hydroxy-4-cholesten-3-one to assist in diagnosis of bile acid malabsorption. Clin Mass Spectrom 2017;3:1–6. https://doi.org/10.1016/j.clinms.2017.02.001.Search in Google Scholar PubMed PubMed Central

36. Lamaziere, A, Rainteau, D, Pukar, KC, Humbert, L, Gauliard, E, Ichou, F, et al.. Distinct postprandial bile acids responses to a high-calorie diet in men volunteers underscore metabolically healthy and unhealthy phenotypes. Nutrients 2020;12. https://doi.org/10.3390/nu12113545.Search in Google Scholar PubMed PubMed Central

37. Hammer, F, Drescher, DG, Schneider, SB, Quinkler, M, Stewart, PM, Allolio, B, et al.. Sex steroid metabolism in human peripheral blood mononuclear cells changes with aging. J Clin Endocrinol Metab 2005;90:6283–9. https://doi.org/10.1210/jc.2005-0915.Search in Google Scholar PubMed

38. Ishida, H, Noshiro, M, Okuda, K, Coon, MJ. Purification and characterization of 7-alpha-hydroxy-4-cholesten-3-one 12-alpha-hydroxylase. J Biol Chem 1992;267:21319–23. https://doi.org/10.1016/s0021-9258(19)36611-6.Search in Google Scholar

39. Griffiths, WJ, Wang, YQ. Oxysterols as lipid mediators: their biosynthetic genes, enzymes and metabolites. Prostaglandins Other Lipid Mediators 2020;147. https://doi.org/10.1016/j.prostaglandins.2019.106381.Search in Google Scholar PubMed PubMed Central

40. Madenspacher, JH, Stapleton, RD, Suratt, BT, Dixon, AE, Lih, FB, Lowe, JM, et al.. Cholestenoic acid is a prognostic biomarker in acute respiratory distress syndrome. J Allergy Clin Immunol 2019;143:440–2. https://doi.org/10.1016/j.jaci.2018.09.017.Search in Google Scholar PubMed PubMed Central

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

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  35. EFLM Task Force Preparation of Labs for Emergencies (TF-PLE) survey on cybersecurity
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https://doi.org/10.1515/cclm-2024-0275
Keywords for this article
LC-MS/MS; 7α-hydroxy-4-cholesten-3-one; bile acid diarrhoea; C4; SeHCAT; bile acid malabsorption

Articles in the same Issue

  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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