Home Medicine Evaluation of the first immunosuppressive drug assay available on a fully automated LC-MS/MS-based clinical analyzer suggests a new era in laboratory medicine
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Evaluation of the first immunosuppressive drug assay available on a fully automated LC-MS/MS-based clinical analyzer suggests a new era in laboratory medicine

  • Sebastian Hörber ORCID logo , Andreas Peter , Rainer Lehmann and Miriam Hoene ORCID logo EMAIL logo
Published/Copyright: October 19, 2020
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 59 Issue 5

Abstract

Objectives

Due to its high specificity, liquid chromatography-tandem mass spectrometry (LC-MS/MS) is considered the gold standard in diagnostic areas such as therapeutic monitoring of immunosuppressive drugs (ISDs). However, many laboratories still rely on immunoassays for ISD quantification in a tradeoff between analytical performance and the advantages of fully automated analyzers – shorter turnaround times, greater ease of use, and 24/7 availability.

Methods

The LC-MS/MS-based Thermo Scientific™ Cascadion™ SM Immunosuppressant Panel was evaluated for >6 months in the routine laboratory of a university hospital. We assessed the analytical performance of the panel and compared it to conventional LC-MS/MS as well as to immunoassays (cyclosporine A, sirolimus, tacrolimus (Siemens) and everolimus (Thermo Fisher)). In addition, both ISD panel and Cascadion analyzer were scrutinized with regards to, e.g., turnaround time, usability, and robustness.

Results

All ISDs showed high linearity and precision (CV≤6%) and a good correlation with conventional LC-MS/MS. The mean deviation to the immunoassays was 17–19% and negative for all ISDs except everolimus with a positive 19% bias. No weak points were revealed when challenging assay and system with, e.g., high haematocrit, sedimented whole blood or priority samples. The Cascadion integrated well into our 24/7 routine and could easily be operated simultaneously with several other analyzers by technical staff without LC-MS experience.

Conclusions

The ISD panel showed excellent analytical performance and demonstrated that a fully automated LC-MS-based analysis starting from primary samples is feasible, suggesting that LC-MS could become an integral part of 24/7 diagnostics in the near future.

Keywords: Cascadion Analyzer; cyclosporine A; everolimus; sirolimus; tacrolimus
Corresponding author: Dr. Miriam Hoene, Department for Diagnostic Laboratory Medicine, Institute for Clinical Chemistry and Pathobiochemistry, University Hospital Tübingen, Hoppe-Seyler-Str. 3, 72076 Tübingen, Germany; and Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany, Phone: +49 7071 29 85676, Email:

Acknowledgments

We thank Isolde Riedlinger and Susanne Faix for excellent technical assistance.

  1. Research funding: None declared.

  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: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: The study was conducted according to the Declaration of Helsinki and approved by the local Ethics Committee of the medical faculty of Tübingen (protocol number: 113/2014BO1).

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2020-0848).

Received: 2020-06-04
Accepted: 2020-10-06
Published Online: 2020-10-19
Published in Print: 2021-04-27

© 2020 Walter de Gruyter GmbH, Berlin/Boston

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  5. Non-invasive determination of uric acid in human saliva in the diagnosis of serious disorders
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  36. Letters to the Editor
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https://doi.org/10.1515/cclm-2020-0848
Keywords for this article
Cascadion Analyzer; cyclosporine A; everolimus; sirolimus; tacrolimus

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Home pregnancy tests: quality first
  4. Review
  5. Non-invasive determination of uric acid in human saliva in the diagnosis of serious disorders
  6. Opinion Papers
  7. Basophil counting in hematology analyzers: time to discontinue?
  8. The role of laboratory hematology between technology and professionalism: the paradigm of basophil counting
  9. Recommendations for validation testing of home pregnancy tests (HPTs) in Europe
  10. General Clinical Chemistry and Laboratory Medicine
  11. The use of preanalytical quality indicators: a Turkish preliminary survey study
  12. The Italian External Quality Assessment (EQA) program on urinary sediment by microscopy examination: a 20 years journey
  13. Non-HDL-C/TG ratio indicates significant underestimation of calculated low-density lipoprotein cholesterol (LDL-C) better than TG level: a study on the reliability of mathematical formulas used for LDL-C estimation
  14. Evaluation of the protein gap for detection of abnormal serum gammaglobulin level: an imperfect predictor
  15. Impact of routine S100B protein assay on CT scan use in children with mild traumatic brain injury
  16. Using machine learning to develop an autoverification system in a clinical biochemistry laboratory
  17. Effect of collection matrix, platelet depletion, and storage conditions on plasma extracellular vesicles and extracellular vesicle-associated miRNAs measurements
  18. Pneumatic tube transportation of urine samples
  19. Evaluation of the first immunosuppressive drug assay available on a fully automated LC-MS/MS-based clinical analyzer suggests a new era in laboratory medicine
  20. A validated LC-MS/MS method for the simultaneous quantification of the novel combination antibiotic, ceftolozane–tazobactam, in plasma (total and unbound), CSF, urine and renal replacement therapy effluent: application to pilot pharmacokinetic studies
  21. Immunosuppressant quantification in intravenous microdialysate – towards novel quasi-continuous therapeutic drug monitoring in transplanted patients
  22. Reference Values and Biological Variations
  23. Reference intervals for venous blood gas measurement in adults
  24. Cardiovascular Diseases
  25. Detection and functional characterization of a novel MEF2A variation responsible for familial dilated cardiomyopathy
  26. Diabetes
  27. Evaluation of the ARKRAY HA-8190V instrument for HbA1c
  28. Infectious Diseases
  29. An original multiplex method to assess five different SARS-CoV-2 antibodies
  30. Evaluation of dried blood spots as alternative sampling material for serological detection of anti-SARS-CoV-2 antibodies using established ELISAs
  31. Variability of cycle threshold values in an external quality assessment scheme for detection of the SARS-CoV-2 virus genome by RT-PCR
  32. The vasoactive peptide MR-pro-adrenomedullin in COVID-19 patients: an observational study
  33. Corrigenda
  34. Corrigendum to: Understanding and managing interferences in clinical laboratory assays: the role of laboratory professionals
  35. Corrigendum to: Age appropriate reference intervals for eight kidney function and injury markers in infants, children and adolescents
  36. Letters to the Editor
  37. A panhaemocytometric approach to COVID-19: a retrospective study on the importance of monocyte and neutrophil population data on Sysmex XN-series analysers
  38. Letter in reply to the letter to the editor of Harte JV and Mykytiv V with the title “A panhaemocytometric approach to COVID-19: a retrospective study on the importance of monocyte and neutrophil population data”
  39. SARS-CoV-2 serologic tests: do not forget the good laboratory practice
  40. Long-term kinetics of anti-SARS-CoV-2 antibodies in a cohort of 197 hospitalized and non-hospitalized COVID-19 patients
  41. Self-sampling at home using volumetric absorptive microsampling: coupling analytical evaluation to volunteers’ perception in the context of a large scale study
  42. Vortex mixing to alleviate pseudothrombocytopenia in a blood specimen with platelet satellitism and platelet clumps
  43. Comparative evaluation of the fully automated HemosIL® AcuStar ADAMTS13 activity assay vs. ELISA: possible interference by autoantibodies different from anti ADAMTS-13
  44. Significant interference on specific point-of-care glucose measurements due to high dose of intravenous vitamin C therapy in critically ill patients
  45. As time goes by, on that you can rely … preservation of urine samples for morphological analysis of erythrocytes and casts
  46. Stability of control materials for α-thalassemia immunochromatographic strip test
  47. Reformulated Architect® cyclosporine CMIA assay: improved imprecision, worse comparability between methods
  48. Urine-to-plasma contamination mimicking acute kidney injury: small drops with major consequences
  49. Automated Mindray CL-1200i chemiluminescent assays of renin and aldosterone for the diagnosis of primary aldosteronism
  50. Use of common reference intervals does not necessarily allow inter-method numerical result trending
  51. Reply to Dr Hawkins regarding comparability of results for monitoring
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