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Evaluation of analytical performance of homocysteine LC-MS/MS assay and design of internal quality control strategy

  • Furong Zhao , Guoliang Pan , Mo Hong , Haipeng Zhao , Mingli Liu , Shuang Wang , Xiaoyu Sun and Yunfeng Cao ORCID logo EMAIL logo
Published/Copyright: January 13, 2023
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 61 Issue 6

Abstract

Objectives

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has become a common technique in clinical laboratories in recent years. Because most methods are laboratory-developed tests (LDTs), their reproducibility and quality control (QC) have been controversial. In this study, Westgard Sigma Rules were used to evaluate the analytical performance and establish an individualised internal QC (IQC) strategy for these LDTs.

Methods

Taking the LC-MS/MS LDT method for homocysteine (Hcy) as an example, the ‘desirable specifications’ from the Biological Variation Database were used as quality goals. Based on the external quality assessment (EQA) samples, bias was calculated and the coefficient of variation (CV) was also calculated by IQC measurements for six consecutive months. The analytical performance was evaluated by calculated sigma metrics and an IQC strategy was designed using the Westgard Sigma Rules with run size.

Results

Over 116 days within 6 months, a total of 850 data points were collected for each of IQC 1 and IQC 2. The monthly coefficient of variation CV% was 2.57–4.01%, which was non-significant (p-value: 0.75). The absolute bias% for IQC1 and IQC2 was 1.23 and 1.87%, respectively. The allowable total error (TEa) was selected as 15.5%, Sigma metrics were 4.02 and 4.30, and the analytical performance was ‘Good’. The 13s/22s/R4s/41s multi rules (n=4, r=1) with a run size of 200 samples were suggested for the Hcy IQC scheme. The quality goal index (QGI) values were over 1.2, indicating that trueness needed to be improved.

Conclusions

The analytical performance of the Hcy LC-MS/MS LDT conformed to the Six Sigma rating level, achieving ‘good’ (four Sigma). Clinical practice indicated that calibration bias was the primary factor affecting trueness.

Keywords: analytical performance; laboratory-developed test; Westgard Sigma Rules with run size
Corresponding author: Yunfeng Cao, Development Platform for Mass Spectrometry Technology, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, P.R. China, E-mail:
Furong Zhao and Guoliang Pan contributed equally to this work.

Funding source: Science and Technology Program of Shenyang

Award Identifier / Grant number: 21-173-9-25

  1. Research funding: Science and Technology Program of Shenyang (21-173-9-25).

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

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

  4. Informed consent: Not applicable.

  5. Ethical approval: Not applicable.

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2022-0805).

Received: 2022-08-17
Accepted: 2022-12-21
Published Online: 2023-01-13
Published in Print: 2023-05-25

© 2023 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2022-0805
Keywords for this article
analytical performance; laboratory-developed test; Westgard Sigma Rules with run size

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Improving access to diagnostic testing in conflict-affected areas: what is needed?
  4. Review
  5. Deciphering the role of monocyte and monocyte distribution width (MDW) in COVID-19: an updated systematic review and meta-analysis
  6. Opinion Paper
  7. From research cohorts to the patient – a role for “omics” in diagnostics and laboratory medicine?
  8. EFLM Paper
  9. The European Register of Specialists in Clinical Chemistry and Laboratory Medicine: code of conduct, version 3 – 2023
  10. Guidelines and Recommendations
  11. Cardiac troponin measurement at the point of care: educational recommendations on analytical and clinical aspects by the IFCC Committee on Clinical Applications of Cardiac Bio-Markers (IFCC C-CB)
  12. Genetics and Molecular Diagnostics
  13. A new and improved method of library preparation for non-invasive prenatal testing: plasma to library express technology
  14. Multiplex proteomics using proximity extension assay for the identification of protein biomarkers predictive of acute graft-vs.-host disease in allogeneic hematopoietic cell transplantation
  15. General Clinical Chemistry and Laboratory Medicine
  16. Assessment of laboratory capacity in conflict-affected low-resource settings using two World Health Organization laboratory assessment tools
  17. Challenge in hyponatremic patients – the potential of a laboratory-based decision support system for hyponatremia to improve patient’s safety
  18. Evaluation of hemolysis, lipemia, and icterus interference with common clinical immunoassays
  19. Serum bicarbonate stability study at room temperature – influence of time to centrifugation and air exposure on bicarbonate measurement reported according to the CRESS checklist
  20. Effects of lipemia on capillary serum protein electrophoresis in native ultra-lipemic material and intravenous lipid emulsion added sera
  21. C-reactive protein interacts with amphotericin B liposomes and its potential clinical consequences
  22. Evaluation of analytical performance of homocysteine LC-MS/MS assay and design of internal quality control strategy
  23. A reliable and high throughput HPLC–HRMS method for the rapid screening of β-thalassemia and hemoglobinopathy in dried blood spots
  24. Dynamics of the vitamin D C3-epimer levels in preterm infants
  25. Comparison of ANA testing by indirect immunofluorescence or solid-phase assays in a low pre-test probability population for systemic autoimmune disease: the Camargo Cohort
  26. Reference Values and Biological Variations
  27. LMS-based continuous reference percentiles for 14 laboratory parameters in the CALIPER cohort of healthy children and adolescents
  28. Indirectly determined reference intervals for automated white blood cell differentials of pediatric patients in Berlin and Brandenburg
  29. Infectious Diseases
  30. Evaluation of a high-sensitivity SARS-CoV-2 antigen test on the fully automated light-initiated chemiluminescent immunoassay platform
  31. Letters to the Editor
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  33. Frozen serum sample pool should not be used as internal quality assessment for lipemia (L) index
  34. Stability of SARS-CoV-2 respiratory samples in non-freezing condition: importance for tropical countries under heavy diagnostic demand
  35. A rare case of both macro-TSH and macro-LH: laboratory analysis of the pathogenesis
  36. A new method for early cancer detection based on platelet transcriptomics will have low positive predictive value
  37. Comparison of near-infrared and UV–vis-based non-contact hematocrit prediction of dried blood spots from patients on immunosuppressants
  38. The diagnostics of heparin-induced thrombocytopenia in Italy and the possible impact of vaccine-induced immune thrombotic thrombocytopenia on it
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  42. 43rd annual conference of the association of clinical biochemists in Ireland (ACBI 2021)
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