title: Five year results of an international proficiency testing programme for measurement of antifungal drug concentrations.
abstract: OBJECTIVE
  Since 2007 the Dutch Association for Quality Assessment in Therapeutic Drug Monitoring (KKGT) has organized an international interlaboratory proficiency testing (PT) programme for measurement of antifungal drugs in plasma. We describe the 5 year results of the laboratories' performance.
  
  
  METHODS
  Twice a year, laboratories received a set of blind plasma samples containing low or high concentrations of fluconazole, itraconazole, hydroxyitraconazole, posaconazole, voriconazole and flucytosine. Participating laboratories were asked to report their results within 6 weeks after dispatch and provide details of their analytical methods. Results deviating >20% from the weighed-in concentration were considered inaccurate. Four-way ANOVA was performed to assess the effect of antifungal drug measured, concentration, analytical method and performing laboratory on the absolute inaccuracy. In 2012, a questionnaire based on the CLSI guidelines was dispatched with the request to provide input on sources of error.
  
  
  RESULTS
  Fifty-seven laboratories (13 countries) reported 2251 results (287 fluconazole, 451 itraconazole, 348 hydroxyitraconazole, 402 posaconazole, 652 voriconazole and 111 flucytosine) in 5 years. Analyses were performed using HPLC (55.0%), LC-MS(/MS) (43.4%), UPLC (1.4%) or GC-MS (0.2%). Overall, 432 (19.2%) analyses were inaccurate. The performing laboratory was the only factor clearly associated with inaccuracies. The questionnaire results indicated that laboratories encounter significant problems analysing low concentrations (15.4% of all inaccuracies).
  
  
  CONCLUSIONS
  Results of the PT programme suggest that one out of five measurements is inaccurate. The performing laboratory is the main determinant of inaccuracy, suggesting that internal quality assurance is pivotal in preventing inaccuracies, irrespective of the antifungal drug measured, concentration and analytical equipment.
authors.affiliation: Radboud University Medical Center, Department of Pharmacy, Radboud Institute for Health Sciences, Nijmegen, The Netherlands.
authors.forename: V J C
authors.initials: VJ
authors.lastname: Lempers
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
authors.forename: J W C
authors.initials: JW
authors.lastname: Alffenaar
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands Dutch Association for Quality Assessment in Therapeutic Drug Monitoring and Clinical Toxicology (KKGT), The Hague, The Netherlands.
authors.forename: D J
authors.initials: DJ
authors.lastname: Touw
authors.affiliation: Radboud University Medical Center, Department of Pharmacy, Radboud Institute for Health Sciences, Nijmegen, The Netherlands.
authors.forename: D M
authors.initials: DM
authors.lastname: Burger
authors.affiliation: Dutch Association for Quality Assessment in Therapeutic Drug Monitoring and Clinical Toxicology (KKGT), The Hague, The Netherlands.
authors.forename: D R A
authors.initials: DR
authors.lastname: Uges
authors.affiliation: Radboud University Medical Center, Department of Pharmacy, Radboud Institute for Health Sciences, Nijmegen, The Netherlands Dutch Association for Quality Assessment in Therapeutic Drug Monitoring and Clinical Toxicology (KKGT), The Hague, The Netherlands.
authors.forename: R E
authors.initials: RE
authors.lastname: Aarnoutse
authors.affiliation: Radboud University Medical Center, Department of Pharmacy, Radboud Institute for Health Sciences, Nijmegen, The Netherlands roger.bruggemann@radboudumc.nl.
authors.forename: R J M
authors.initials: RJ
authors.lastname: Brüggemann
mesh_terms: D000935:Antifungal Agents / Q000097:blood*; D016903:Drug Monitoring / Q000379:methods / Q000592:standards*; D006801:Humans; D038622:Internationality; D059021:Laboratory Proficiency Testing / Q000379:methods / Q000592:standards*; D008826:Microbial Sensitivity Tests / Q000379:methods / Q000592:standards; D016037:Single-Blind Method; D013997:Time Factors
chemical_list: D000935:Antifungal Agents
keywords: analytical method; pharmacokinetics; therapeutic drug monitoring