Lempers V J C, Alffenaar J W C, Touw D J, Burger D M, Uges D R A, Aarnoutse R E, Brüggemann R J M
Radboud University Medical Center, Department of Pharmacy, Radboud Institute for Health Sciences, Nijmegen, The Netherlands.
Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
J Antimicrob Chemother. 2014 Nov;69(11):2988-94. doi: 10.1093/jac/dku242. Epub 2014 Jul 7.
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.
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.
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).
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.
自2007年起，荷兰治疗药物监测质量评估协会（KKGT）组织了一项国际实验室间能力验证（PT）计划，用于检测血浆中的抗真菌药物。我们描述了各实验室5年的表现结果。
实验室每年接收两次盲法血浆样本，其中含有低浓度或高浓度的氟康唑、伊曲康唑、羟基伊曲康唑、泊沙康唑、伏立康唑和氟胞嘧啶。要求参与实验室在样本发送后6周内报告结果，并提供其分析方法的详细信息。与称重浓度偏差超过20%的结果被视为不准确。进行四因素方差分析，以评估所测抗真菌药物、浓度、分析方法和执行实验室对绝对误差的影响。2012年，发放了一份基于CLSI指南的调查问卷，要求提供有关误差来源的信息。
57个实验室（来自13个国家）在5年中报告了2251项结果（287项氟康唑、451项伊曲康唑、348项羟基伊曲康唑、402项泊沙康唑、652项伏立康唑和111项氟胞嘧啶）。分析采用高效液相色谱法（HPLC，55.0%）、液相色谱-质谱联用（LC-MS(/MS)，43.4%）、超高效液相色谱法（UPLC，1.4%）或气相色谱-质谱联用（GC-MS，0.2%）。总体而言，432项（19.2%）分析不准确。执行实验室是唯一与不准确结果明显相关的因素。调查问卷结果表明，实验室在分析低浓度样本时遇到了重大问题（占所有不准确结果的15.4%）。
能力验证计划的结果表明，五分之一的测量结果不准确。执行实验室是误差的主要决定因素，这表明内部质量保证对于防止误差至关重要，无论所测抗真菌药物、浓度和分析设备如何。
