title: Liquid chromatography-tandem mass spectrometry method for simultaneous quantification of four triazole antifungal agents in human plasma.
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.
authors.affiliation: Biological Pharmacology and Toxicology, University Hospital, Rennes 1 University, Rennes, France.
authors.forename: Marie-Clémence
authors.initials: MC
authors.lastname: Verdier
authors.forename: Danièle
authors.initials: D
authors.lastname: Bentué-Ferrer
authors.forename: Olivier
authors.initials: O
authors.lastname: Tribut
authors.forename: Eric
authors.initials: E
authors.lastname: Bellissant
mesh_terms: D000935:Antifungal Agents / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D053719:Tandem Mass Spectrometry; D014230:Triazoles / Q000097:blood*
chemical_list: D000935:Antifungal Agents; D014230:Triazoles