Startseite Quantification of linezolid in serum by LC-MS/MS using semi-automated sample preparation and isotope dilution internal standardization
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Quantification of linezolid in serum by LC-MS/MS using semi-automated sample preparation and isotope dilution internal standardization

  • Johannes Zander EMAIL logo , Barbara Maier , Michael Zoller , Daniel Teupser und Michael Vogeser
Veröffentlicht/Copyright: 25. Oktober 2013
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Clinical Chemistry and Laboratory Medicine (CCLM)
Aus der Zeitschrift Clinical Chemistry and Laboratory Medicine (CCLM) Band 52 Heft 3

Abstract

Background: Linezolid serum concentrations have been shown to be highly variable in critically ill patients with often sub-therapeutic drug levels regarding minimal inhibitory concentrations for relevant pathogens. Consequently, therapeutic drug monitoring of linezolid must be considered, requiring a reliable and convenient analytical method. We therefore developed and validated an LC-MS/MS method applying isotope dilution internal standardization and on-line solid phase extraction for serum linezolid quantification.

Methods: Sample preparation was based on protein precipitation and on-line solid phase extraction with two-dimensional liquid chromatography and column switching. Three-fold deuterated linezolid was used as the internal standard. The method was validated involving two separate LC-MS/MS systems covering the concentration range of 0.13–32 mg/L. The run time was 4 min.

Results: Validation revealed good analytical performance, with inaccuracy <6% and imprecision of <7.3% (CV) for six quality control samples (0.38–16.0 mg/L). The method was found to be robust during the validation process and during a pharmacokinetic study so far involving 600 samples. Comparative measurements on two LC-MS/MS systems revealed close agreement.

Conclusions: This LC-MS/MS assay described herein is a convenient, robust and reliable method for linezolid quantification in serum which can be routinely applied using different LC-MS/MS systems. The method can be used for clinical studies and subsequent TDM of linezolid.

Keywords : linezolid; liquid chromatography tandem mass spectrometry (LC-MS/MS); mass spectrometry; on-line solid phase extraction; serum; therapeutic drug monitoring; Conversion factor of linezolid: [mg/L]×2.96→[µmol/L]
Corresponding author: Johannes Zander, Institute of Laboratory Medicine, Hospital of the University of Munich, Marchioninistrasse 15, 81377 Munich, Germany, Phone: +49 89 70953231, E-mail:

This study was supported by a Mérieux Research Grant (Institut Mérieux, Lyon, France).

Conflict of interest statement

Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article. Research support played no role in the study design; in the collection, analyzis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared

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Received: 2013-07-26
Accepted: 2013-09-23
Published Online: 2013-10-25
Published in Print: 2014-03-01

©2014 by Walter de Gruyter Berlin Boston

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https://doi.org/10.1515/cclm-2013-0594
Schlagwörter für diesen Artikel
linezolid; liquid chromatography tandem mass spectrometry (LC-MS/MS); mass spectrometry; on-line solid phase extraction; serum; therapeutic drug monitoring; Conversion factor of linezolid: [mg/L]×2.96→[µmol/L]

Artikel in diesem Heft

  1. Masthead
  2. Masthead
  3. Editorial
  4. Point of care testing: evolving scenarios and innovative perspectives
  5. Review
  6. Point-of-care testing: where is the evidence? A systematic survey
  7. Mini Review
  8. Vulnerability of point-of-care test reagents and instruments to environmental stresses: implications for health professionals and developers
  9. Opinion Paper
  10. Twenty-five years of idiopathic calcium nephrolithiasis: has anything changed?
  11. Genetics and Molecular Diagnostics
  12. Optimizing the purification and analysis of miRNAs from urinary exosomes
  13. General Clinical Chemistry and Laboratory Medicine
  14. Extensive study of human insulin immunoassays: promises and pitfalls for insulin analogue detection and quantification
  15. Absorptive chemistry based extraction for LC-MS/MS analysis of small molecule analytes from biological fluids – an application for 25-hydroxyvitamin D
  16. Evaluation of 3-epi-25-hydroxyvitamin D3 cross-reactivity in the Roche Elecsys Vitamin D Total protein binding assay
  17. Quantification of linezolid in serum by LC-MS/MS using semi-automated sample preparation and isotope dilution internal standardization
  18. Comparison of two immunoassays for measurement of faecal calprotectin in detection of inflammatory bowel disease: (pre)-analytical and diagnostic performance characteristics
  19. Reference Values and Biological Variations
  20. Reference change values to assess changes in concentrations of biomarkers of exposure in individuals participating in a cigarette-switching study
  21. Reference values of fetal serum β2-microglobulin in the Chinese: evaluation of its clinical usefulness
  22. Cancer Diagnostics
  23. Gut neuroendocrine tumor blood qPCR fingerprint assay: characteristics and reproducibility
  24. Androgen deprivation decreases prostate specific antigen in the absence of tumor: implications for interpretation of PSA results
  25. Radioimmunoassay of free plasma metanephrines for the diagnosis of catecholamine-producing tumors
  26. Infectious Diseases
  27. Plasma endothelial cell-specific molecule-1 (ESM-1) in management of community-acquired pneumonia
  28. A soluble form of the macrophage-related mannose receptor (MR/CD206) is present in human serum and elevated in critical illness
  29. Letters to the Editor
  30. Evaluation of a JAK2 V617F quantitative PCR to monitor residual disease post-allogeneic hematopoietic stem cell transplantation for myeloproliferative neoplasms
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  32. Clinical sample stability and measurement uncertainty
  33. A specific and sensitive activated partial thromboplastin time (APTT)-based factor VIII inhibitor screening assay
  34. Evaluating the inappropriateness of repeated laboratory testing in a teaching hospital of South Italy
  35. Could kidney glomerular filtration impairment represent the “Achilles heel” of HE4 serum marker? A possible further implication
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