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Liquid chromatography-tandem mass spectrometry method for simultaneous quantification of four triazole antifungal agents in human plasma

  • Marie-Clémence Verdier , Danièle Bentué-Ferrer , Olivier Tribut and Eric Bellissant
Published/Copyright: June 18, 2010
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Clinical Chemistry and Laboratory Medicine
From the journal Clinical Chemistry and Laboratory Medicine Volume 48 Issue 10

Abstract

Background: Invasive fungal infections are an increasing cause of morbidity and mortality. Triazole antifungal agents are recommended for the prevention and treatment of such infections. Their broad inter- and intra-individual pharmacokinetic variability and the high probability of drug-drug interactions justify therapeutic drug monitoring (TDM). We developed a liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of four triazole antifungal agents (fluconazole, itraconazole, posaconazole, voriconazole) and one of their metabolites (hydroxy-itraconazole) in human plasma.

Methods: After protein precipitation with acetonitrile (ACN), a C18 column was used for separation with a mobile phase consisting of 0.1% formic acid, water and ACN in a linear gradient from 20% to 70%, over 10 min. Detection was performed by electrospray ionization and quantification was performed using selected reaction monitoring transitions.

Results: Total run time was 15 min. The method was validated for a range of 0.1–12 μg/mL. Coefficients of variation were <9.5% and <13.8%, and accuracies were between –5.4% and +7.7% and between –10.8% and +10.4%, for intra- and inter-day validations, respectively.

Conclusions: This method appears to be well suited to routine hospital practice for the TDM of triazole antifungal agents considering its time of analysis, range of concentrations measured, precision and accuracy.

Clin Chem Lab Med 2010;48:1515–22.

Keywords: antifungal agents; liquid chromatography-mass spectrometry (LC-MS/MS); therapeutic drug monitoring (TDM)
Corresponding author: Danièle Bentué-Ferrer, Service de Pharmacologie Biologique – Toxicologie, CHU de Rennes, Hôpital de Pontchaillou, 2 Rue Henri Le Guilloux, 35033 Rennes Cedex, France Phone: +33 2 23 23 47 13, Fax: +33 2 23 23 46 05,
Received: 2010-1-25
Accepted: 2010-4-15
Published Online: 2010-06-18
Published in Print: 2010-10-01

©2010 by Walter de Gruyter Berlin New York

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https://doi.org/10.1515/CCLM.2010.252
Keywords for this article
antifungal agents; liquid chromatography-mass spectrometry (LC-MS/MS); therapeutic drug monitoring (TDM)

Articles in the same Issue

  1. Editorial
  2. Darwinian evolution or regression? The fate of laboratory professionals
  3. Review
  4. Automated reticulocyte counting: state of the art and clinical applications in the evaluation of erythropoiesis
  5. Minireview
  6. Laboratory diagnostics in acute poisoning: critical overview
  7. Opinion Papers
  8. On the origins of physicians: Darwinian or Lamarckian evolution?
  9. Observed, unknown distributions of clinical chemical quantities should be considered to be log-normal: a proposal
  10. Guidelines and Recommendations
  11. Development and description of GETT: a Genetic testing Evidence Tracking Tool
  12. Genetics and Molecular Diagnostics
  13. DNA sequencing errors in molecular diagnostics of filamin myopathy
  14. High resolution melting for the identification of mutations in the iron responsive element of the ferritin light chain gene
  15. General Clinical Chemistry and Laboratory Medicine
  16. Detection of serum free light chains: the problem with antigen excess
  17. Hepcidin concentrations and iron homeostasis in preeclampsia
  18. Automated assay for non-transferrin-bound iron in serum samples
  19. A simple liquid chromatography-tandem mass spectrometry method for urinary free cortisol analysis: suitable for routine purpose
  20. Evaluation of a multiplex assay for adipokine concentrations in obese children
  21. The use of serial patient blood gas, electrolyte and glucose results to derive biologic variation: a new tool to assess the acceptability of intensive care unit testing
  22. Point-of-care determination of neonatal bilirubin with the blood gas analyzer RapidLab 1265
  23. The effect of pre-analytical variables on light transmittance aggregometry in citrated platelet-rich plasma from healthy subjects
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  25. Clinical significance of serum macrophage-colony stimulating factor (M-CSF) in esophageal cancer patients and its comparison with classical tumor markers
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  27. Serum soluble tumour necrosis factor receptor type I concentrations independently predict prognosis in patients with breast cancer
  28. Variations in systemic biomarkers of oxidative/nitrosative stress and DNA damage before and during the consequent two cycles of chemotherapy in breast cancer patients
  29. Spurious increase in serum chromogranin A: the role of heterophilic antibodies
  30. Infectious Diseases
  31. Identification and evaluation of a new nucleic acid amplification test target for specific detection of Mycobacterium tuberculosis
  32. Application of an oligonucleotide microarray-based nano-amplification technique for the detection of fungal pathogens
  33. Liquid chromatography-tandem mass spectrometry method for simultaneous quantification of four triazole antifungal agents in human plasma
  34. Evaluation of two sirolimus assays using the ARCHITECT-i1000® CMIA or RxL® ACMIA methods in comparison with the IMx® MEIA method
  35. Widespread use of point-of-care testing is irreconcilable with the present-day quest for safety
  36. Congress Abstracts
  37. 3rd Annual Congress of the Austrian Society for Laboratory Medicine and Clinical Chemistry Salzburg, Austria, 27-30 October 2010
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