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Add-on testing: stability assessment of 63 biochemical analytes in centrifuged and capped samples stored at 16 °C

  • Anne J. Nielsen EMAIL logo , Søren A. Ladefoged and Jeppe B. Madsen
Published/Copyright: April 10, 2024
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 62 Issue 9

Abstract

Objectives

Integration of add-on testing in high-scale automated clinical laboratories constitute a valuable instrument not only for the clinicians and the general patient care, but also for the laboratory itself. Knowledge on sample quality and analytical stability upon storage is necessary to be able to offer add-on testing. The objectives of this study were to examine the analytical stability of 63 biochemical analytes in plasma and urine samples stored at 16 °C.

Methods

Samples were collected by professional laboratory technicians, analyzed at automated analyzers and stored in their primary, capped tube without separator for 10, 12, 16, 20 or 24 h at 16 °C. Stability was assessed by inspecting mean concentration of samples at baseline and examining if (A) mean concentration over time violated limits of bias, or if (B) individual sample concentrations violated limits of total error.

Results

The majority of the 63 analytes were stable for up to 24 h of storage. Few of the analytes were only suitable for add-on testing for 4, 6, 10, 12, 16 or 20 h of storage. One analyte, P-lactate dehydrogenase, was not found suitable for add-on testing when stored at 16 °C.

Conclusions

Due to the increasing number of intelligent solutions for high-scale clinical laboratories, add-on testing has come to stay. Loss of stability could not be demonstrated for the majority of analytes after 10, 12, 16, 20 or 24 h of storage. This feature of analytical stability suggests that add-on testing is an acceptable tool for these analytes.

Keywords: add-on testing; stability assessment; postanalytical; plasma; urine; capped tubes
Corresponding author: Anne J. Nielsen, Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark; and Department of Clinical Medicine, Aarhus University, Aarhus, Denmark, E-mail:

Acknowledgments

The authors wish to thank Charlotte Hejlesen and Ulrik Byskov Larsen for exceptional technical assistance and head laboratory technician Lotte Kristine Cornelius Lassen for logistic and organisational support.

  1. Research ethics: The study was a quality assurance project, and no further ethical approval was needed according to national regulations and institutional policies.

  2. Informed consent: Oral consent was received from all participants.

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

  4. Competing interests: Authors state no conflict of interest.

  5. Research funding: None declared.

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

References

1. Guder, WG, da Fonseca-Wollheim, F, Heil, W, Schmitt, Y, Töpfer, G, Wisser, H, et al.. Quality of diagnostic samples, 3rd completely revised edition ed Oxford: BD Diagnostics; 2010.Search in Google Scholar

2. Sciacovelli, L, Aita, A, Padoan, A, Pelloso, M, Antonelli, G, Piva, E, et al.. Performance criteria and quality indicators for the post-analytical phase. Clin Chem Lab Med 2016;54:1169–76. https://doi.org/10.1515/cclm-2015-0897.Search in Google Scholar PubMed

3. Gomez-Rioja, R, Meyer, AV, Cornes, M, Costelloe, S, Vermeersch, P, Simundic, A-M, et al.. Recommendation for the design of stability studies on clinical specimens. Clin Chem Lab Med 2023;61:1708–18. https://doi.org/10.1515/cclm-2023-0221.Search in Google Scholar PubMed

4. Åsberg KBS, A, Mikkelsen, G. Prøvematerialets holdbarhet – kriterier og vurderinger. Klinisk Biokemi i Norden 2011;23:34–8.Search in Google Scholar

5. Hedayati, M, Razavi, SA, Boroomand, S, Kheradmand Kia, S. The impact of pre-analytical variations on biochemical analytes stability: a systematic review. J Clin Lab Anal 2020;34:e23551. https://doi.org/10.1002/jcla.23551.Search in Google Scholar PubMed PubMed Central

6. Cornes, M, Simundic, A-M, Cadamuro, J, Costelloe, SJ, Baird, G, Kristensen, GBB, et al.. The CRESS checklist for reporting stability studies: on behalf of the European federation of clinical chemistry and laboratory medicine (EFLM) working group for the preanalytical phase (WG-PRE). Clin Chem Lab Med 2021;59:59–69. https://doi.org/10.1515/cclm-2020-0061.Search in Google Scholar PubMed

7. Boyanton, BLJr., Blick, KE. Stability studies of twenty-four analytes in human plasma and serum. Clin Chem 2002;48:2242–7. https://doi.org/10.1093/clinchem/48.12.2242.Search in Google Scholar

8. Clark, S, Youngman, LD, Palmer, A, Parish, S, Peto, R, Collins, R. Stability of plasma analytes after delayed separation of whole blood: implications for epidemiological studies. Int J Epidemiol 2003;32:125–30. https://doi.org/10.1093/ije/dyg023.Search in Google Scholar PubMed

9. Cuhadar, S, Atay, A, Koseoglu, M, Dirican, A, Hur, A. Stability studies of common biochemical analytes in serum separator tubes with or without gel barrier subjected to various storage conditions. Biochem Med 2012;22:202–14. https://doi.org/10.11613/bm.2012.023.Search in Google Scholar PubMed PubMed Central

10. Dupuy, AM, Badiou, S, Daubin, D, Bargnoux, AS, Magnan, C, Klouche, K, et al.. Comparison of Barricor™ vs. lithium heparin tubes for selected routine biochemical analytes and evaluation of post centrifugation stability. Biochem Med 2018;28:020902. https://doi.org/10.11613/bm.2018.020902.Search in Google Scholar

11. Dupuy, AM, Cristol, JP, Vincent, B, Bargnoux, AS, Mendes, M, Philibert, P, et al.. Stability of routine biochemical analytes in whole blood and plasma/serum: focus on potassium stability from lithium heparin. Clin Chem Lab Med 2018;56:413–21. https://doi.org/10.1515/cclm-2017-0292.Search in Google Scholar PubMed

12. Gawria, G, Tillmar, L, Landberg, E. A comparison of stability of chemical analytes in plasma from the BD Vacutainer(®) Barricor™ tube with mechanical separator versus tubes containing gel separator. J Clin Lab Anal 2020;34:e23060. https://doi.org/10.1002/jcla.23060.Search in Google Scholar PubMed PubMed Central

13. Haslacher, H, Szekeres, T, Gerner, M, Ponweiser, E, Repl, M, Wagner, OF, et al.. The effect of storage temperature fluctuations on the stability of biochemical analytes in blood serum. Clin Chem Lab Med 2017;55:974–83. https://doi.org/10.1515/cclm-2016-0608.Search in Google Scholar PubMed

14. Jackson, C, Best, N, Elliott, P. UK Biobank Pilot Study: stability of haematological and clinical chemistry analytes. Int J Epidemiol 2008;37:i16–22. https://doi.org/10.1093/ije/dym280.Search in Google Scholar PubMed

15. Monneret, D, Godmer, A, Le Guen, R, Bravetti, C, Emeraud, C, Marteau, A, et al.. Stability of routine biochemical analytes in whole blood and plasma from lithium heparin gel tubes during 6-h storage. J Clin Lab Anal 2016;30:602–9. https://doi.org/10.1002/jcla.21909.Search in Google Scholar PubMed PubMed Central

16. Peakman, TC, Elliott, P. The UK Biobank sample handling and storage validation studies. Int J Epidemiol 2008;37:i2–6. https://doi.org/10.1093/ije/dyn019.Search in Google Scholar PubMed

17. Nielsen, BK, Frederiksen, T, Friis-Hansen, L, Larsen, PB. Post-analytical stability of 23 common chemistry and immunochemistry analytes in incurred samples. Clin Biochem 2017;50:1175–82. https://doi.org/10.1016/j.clinbiochem.2017.08.003.Search in Google Scholar PubMed

18. Oddoze, C, Lombard, E, Portugal, H. Stability study of 81 analytes in human whole blood, in serum and in plasma. Clin Biochem 2012;45:464–9. https://doi.org/10.1016/j.clinbiochem.2012.01.012.Search in Google Scholar PubMed

19. Kachhawa, K, Kachhawa, P, Varma, M, Behera, R, Agrawal, D, Kumar, S. Study of the stability of various biochemical analytes in samples stored at different predefined storage conditions at an accredited laboratory of India. J Lab Physicians 2017;9:11–15. https://doi.org/10.4103/0974-2727.187928.Search in Google Scholar PubMed PubMed Central

20. Kocijancic, M, Cargonja, J, Delic-Knezevic, A. Evaluation of the BD Vacutainer(®) RST blood collection tube for routine chemistry analytes: clinical significance of differences and stability study. Biochem Med 2014;24:368–75. https://doi.org/10.11613/bm.2014.039.Search in Google Scholar PubMed PubMed Central

21. Leino, A, Koivula, MK. Stability of chemical and immunochemical analytes in uncentrifuged plasma samples. Ann Clin Biochem 2009;46:159–61. https://doi.org/10.1258/acb.2008.008212.Search in Google Scholar PubMed

22. Mathew, G, Zwart, SR, Smith, SM. Stability of blood analytes after storage in BD SST tubes for 12 month. Clin Biochem 2009;42:1732–4. https://doi.org/10.1016/j.clinbiochem.2009.07.015.Search in Google Scholar PubMed

23. Shimizu, Y, Ichihara, K. Elucidation of stability profiles of common chemistry analytes in serum stored at six graded temperatures. Clin Chem Lab Med 2019;57:1388–96. https://doi.org/10.1515/cclm-2018-1109.Search in Google Scholar PubMed

24. Tanner, M, Kent, N, Smith, B, Fletcher, S, Lewer, M. Stability of common biochemical analytes in serum gel tubes subjected to various storage temperatures and times pre-centrifugation. Ann Clin Biochem 2008;45:375–9. https://doi.org/10.1258/acb.2007.007183.Search in Google Scholar PubMed

25. Taylor, EC, Sethi, B. Stability of 27 biochemistry analytes in storage at a range of temperatures after centrifugation. Br J Biomed Sci 2011;68:147–57. https://doi.org/10.1080/09674845.2011.11730343.Search in Google Scholar PubMed

26. van Balveren, JA, Gemen, EFA, Kusters, R. Recentrifugation of lithium heparin gel separator tubes up to 8 h after blood collection has No relevant influence on the stability of 30 routine biochemical analytes. J Appl Lab Med 2019;3:864–9. https://doi.org/10.1373/jalm.2018.026567.Search in Google Scholar PubMed

27. Zwart, SR, Wolf, M, Rogers, A, Rodgers, S, Gillman, PL, Hitchcox, K, et al.. Stability of analytes related to clinical chemistry and bone metabolism in blood specimens after delayed processing. Clin Biochem 2009;42:907–10. https://doi.org/10.1016/j.clinbiochem.2009.02.010.Search in Google Scholar PubMed

28. van Eijsden, M, van der Wal, MF, Hornstra, G, Bonsel, GJ. Can whole-blood samples be stored over 24 hours without compromising stability of C-reactive protein, retinol, ferritin, folic acid, and fatty acids in epidemiologic research? Clin Chem 2005;51:230–2. https://doi.org/10.1373/clinchem.2004.042234.Search in Google Scholar PubMed

29. Kift, RL, Byrne, C, Liversidge, R, Babbington, F, Knox, C, Binns, J, et al.. The effect of storage conditions on sample stability in the routine clinical laboratory. Ann Clin Biochem 2015;52:675–9. https://doi.org/10.1177/0004563215580000.Search in Google Scholar PubMed

30. Vercruysse, K, Lambrecht, S, Oyaert, M. Total lab automation: sample stability of clinical chemistry parameters in an automated storage and retrieval module. Clin Chem Lab Med 2022;60:52–9. https://doi.org/10.1515/cclm-2021-0866.Search in Google Scholar PubMed

31. Biswas, SS, Bindra, M, Jain, V, Gokhale, P. Evaluation of imprecision, bias and total error of clinical chemistry analysers. Indian J Clin Biochem 2015;30:104–8. https://doi.org/10.1007/s12291-014-0448-y.Search in Google Scholar PubMed PubMed Central

32. Schytte, T, Jørgensen, LGM, Brandslund, I, Petersen, PH, Andersen, B The clinical impact of screening for gestational diabetes. Clin Chem Lab Med 2004;42:1036–42.10.1515/CCLM.2004.209Search in Google Scholar PubMed

33. Koch, CG, Reineks, EZ, Tang, AS, Hixson, ED, Phillips, S, Sabik, JF3rd, et al.. Contemporary bloodletting in cardiac surgical care. Ann Thorac Surg 2015;99:779–84. https://doi.org/10.1016/j.athoracsur.2014.09.062.Search in Google Scholar PubMed

34. Hansen, MF, Munk, JK, Lind, B, Bathum, L, Buhl, H, Jørgensen, HL. Hospital-acquired anemia among patients in a university hospital and the affiliated general practices in the capital region of Denmark, 2019. Scand J Clin Lab Investig 2022;82:277–82. https://doi.org/10.1080/00365513.2022.2090433.Search in Google Scholar PubMed

35. López, MG, Roca, NR, Velasco, MS, Martín, MJA, Soto, AB, Rioja, RG. Stability of lactate dehydrogenase in plasma at different temperatures: post-analytical storage. Adv Lab Med 2020;1:20200077. https://doi.org/10.1515/almed-2020-0077.Search in Google Scholar PubMed PubMed Central

36. Nelson, LS, Davis, SR, Humble, RM, Kulhavy, J, Aman, DR, Krasowski, MD. Impact of add-on laboratory testing at an academic medical center: a five year retrospective study. BMC Clin Pathol 2015;15:11. https://doi.org/10.1186/s12907-015-0011-7.Search in Google Scholar PubMed PubMed Central

37. Melanson, SF, Hsieh, B, Flood, JG, Lewandrowski, KB. Evaluation of add-on testing in the clinical chemistry laboratory of a large academic medical center: operational considerations. Arch Pathol Lab Med 2004;128:885–9. https://doi.org/10.5858/2004-128-885-eoatit.Search in Google Scholar

38. Bowen, RA, Remaley, AT. Interferences from blood collection tube components on clinical chemistry assays. Biochem Med 2014;24:31–44. https://doi.org/10.11613/bm.2014.006.Search in Google Scholar

39. Mikesh, LM, Bruns, DE. Stabilization of glucose in blood specimens: mechanism of delay in fluoride inhibition of glycolysis. Clin Chem 2008;54:930–2. https://doi.org/10.1373/clinchem.2007.102160.Search in Google Scholar PubMed

Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/cclm-2023-1388).

Received: 2023-12-02
Accepted: 2024-03-16
Published Online: 2024-04-10
Published in Print: 2024-08-27

© 2024 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2023-1388
Keywords for this article
add-on testing; stability assessment; postanalytical; plasma; urine; capped tubes

Articles in the same Issue

  1. Frontmatter
  2. Editorials
  3. EFLM European Urinalysis Guideline
  4. Clinical Chemistry Laboratory Medicine in the post-acute COVID-19 era
  5. EFLM Guideline
  6. The EFLM European Urinalysis Guideline 2023
  7. Review
  8. Approaching sustainability in Laboratory Medicine
  9. Opinion Papers
  10. New reimbursement models to promote better patient outcomes and overall value in laboratory medicine and healthcare
  11. Screening for sickle cell disease: focus on newborn investigations
  12. Genetics and Molecular Diagnostics
  13. The role of Killer immunoglobulin-like receptors (KIRs) in the genetic susceptibility to non-celiac wheat sensitivity (NCWS)
  14. General Clinical Chemistry and Laboratory Medicine
  15. Understanding the limitations of your assay using EQA data with serum creatinine as an example
  16. Add-on testing: stability assessment of 63 biochemical analytes in centrifuged and capped samples stored at 16 °C
  17. Smartphone swabs as an emerging tool for toxicology testing: a proof-of-concept study in a nightclub
  18. Allergy: Evaluation of 16 years (2007–2022) results of the shared external quality assessment program in Belgium, Finland, Portugal and The Netherlands
  19. Cancer Diagnostics
  20. Monoclonal whole IgG impairs both fibrin and thrombin formation: hemostasis and surface plasmon resonance studies
  21. Cardiovascular Diseases
  22. Patients with antiphospholipid syndrome and a first venous or arterial thrombotic event: clinical characteristics, antibody profiles and estimate of the risk of recurrence
  23. Letters to the Editor
  24. Familial dysalbuminemic hyperthyroxinemia coexisting with a Grave’s disease: a Belgian case report
  25. Diagnostic challenge between a frequent polygenic hypocholesterolemia and an unusual Smith Lemli Opitz syndrome related to bi-allelic DHCR7 mutations
  26. First reported co-occurrence of Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia with pseudo Chediak-Higashi anomaly and complex karyotype
  27. Facing the new IVD Regulation 2017/746: Contract Research Organizations (CROs), key partners of IVDs manufacturers for compliance
  28. Comprehensive analysis and clinical case studies on pseudoeosinophilia: insights and implications – unraveling the complexity: analytical approaches and clinical significance
  29. Misdiagnosis of type 2B von Willebrand disease as immune thrombocytopenia in a thrombocytopenic patient
  30. Biological matrices, reagents and turnaround-time: the full-circle of artificial intelligence in the pre-analytical Phase. Comment on Turcic A, et al., Machine learning to optimize cerebrospinal fluid dilution for analysis of MRZH reaction. CCLM 2024;62:436–41
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