Toxicology Unit, Department of Clinical Biochemistry, King's College Hospital NHS Foundation Trust, Denmark Hill, London, SE5 9RS, UK.
Anal Bioanal Chem. 2012 Aug;404(2):513-23. doi: 10.1007/s00216-012-6176-3. Epub 2012 Jun 14.
Azole antifungal drugs are important in the prophylaxis and treatment of invasive aspergillosis. Therapeutic drug monitoring may be indicated to (1) monitor adherence, (2) guide dosage and (3) minimise the risk of drug-drug interactions and dose-related toxicity. TurboFlow(TM) technology offers online, automated sample preparation. An Aria Transcend(TM) TLX-II coupled with a TSQ Vantage(TM) MS was used. Centrifuged samples (25 μL) were mixed with internal standard solution (975 μL) and 30 μL injected directly onto a C18-P-XL TurboFlow column. Analytes were focussed onto a Phenomenex Gemini Phenyl analytical column and eluted using a methanol/water gradient (flow-rate, 0.8 mL/min). Analytes were monitored in selected reaction monitoring mode (two transitions per analyte, positive mode APCI). Calibration ranges were as follows: itraconazole, hydroxyitraconazole, and posaconazole 0.05-5.0 mg/L; voriconazole and fluconazole 0.1-10 mg/L. Total analysis time was 12 min. TurboFlow column recovery was >77% for all analytes. Calibration was linear (R (2) > 0.99) for all analytes. Inter- and intra-assay imprecision (% RSD) was <8% and accuracy (nominal internal quality control values) 90-105% for all analytes. The limit of detection was 0.01 mg/L for all analytes. No matrix effects were observed. This method is simple, robust and suitable for measuring these compounds at concentrations attained during therapy.
唑类抗真菌药物在侵袭性曲霉菌病的预防和治疗中非常重要。治疗药物监测可能有助于：（1）监测依从性；（2）指导剂量；（3）最大限度地降低药物-药物相互作用和剂量相关毒性的风险。TurboFlow（TM）技术提供在线自动化样品制备。使用 Aria Transcend（TM）TLX-II 与 TSQ Vantage（TM）MS 联用。离心后的样品（25 μL）与内标溶液（975 μL）混合，直接进样到 C18-P-XL TurboFlow 柱上。分析物被聚焦到 Phenomenex Gemini Phenyl 分析柱上，并使用甲醇/水梯度洗脱（流速为 0.8 mL/min）。分析物在选择反应监测模式下进行监测（每个分析物两个转换，正模式 APCI）。校准范围如下：伊曲康唑、羟基伊曲康唑和泊沙康唑 0.05-5.0 mg/L；伏立康唑和氟康唑 0.1-10 mg/L。总分析时间为 12 分钟。TurboFlow 柱的回收率大于所有分析物的 77%。所有分析物的校准均呈线性（R（2）> 0.99）。所有分析物的批内和批间精密度（%RSD）均<8%，准确度（名义内部质量控制值）为 90-105%。所有分析物的检测限均为 0.01 mg/L。未观察到基质效应。该方法简单、稳健，适用于测量治疗期间达到的这些化合物的浓度。
