Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Infectious Diseases, University of Turin, Amedeo di Savoia Hospital, Corso Svizzera 164, 10149 Turin, Italy.
J Antimicrob Chemother. 2012 Nov;67(11):2645-9. doi: 10.1093/jac/dks285. Epub 2012 Aug 7.
Therapeutic drug monitoring (TDM) of triazoles is widely used in clinical practice to optimize therapy. TDM is limited by technical problems and cost considerations, such as sample storage and dry-ice shipping. We aimed to develop and validate a new method to analyse itraconazole, posaconazole and voriconazole in plasma spotted on dry sample spot devices (DSSDs) and to quantify them by an HPLC system.
Extraction from DSSDs was done using n-hexane/ethyl acetate and ammonia solution. Samples were analysed using HPLC with mass spectrometry (HPLC-MS). Accuracy and precision were assayed by inter- and intra-day validation. The stability of triazoles in plasma spotted on DSSDs was investigated at room temperature for 1 month. The method was compared with a validated standard HPLC method for quantification of triazoles in human plasma.
Mean inter- and intra-day accuracy and precision were <15% for all compounds. Triazoles were stable for 2 weeks at room temperature. The method was linear (r(2) > 0.999) in the range 0.031-8 mg/L for itraconazole and posaconazole, and 0.058-15 mg/L for voriconazole. High sensitivity was observed; limits of detection were 0.008, 0.004 and 0.007 mg/L for itraconazole, posaconazole and voriconazole, respectively. A high degree of correlation (r(2) > 0.94) was obtained between the DSSD method and the standard method of analysis.
The method that we developed and validated to quantify triazoles in human plasma spotted on DSSDs is accurate and precise. It overcomes problems related to plasma sample storage and shipment, allowing TDM to be performed in a cheaper and safer manner.
三唑类药物的治疗药物监测（TDM）在临床实践中被广泛用于优化治疗。TDM 受到技术问题和成本考虑的限制，例如样本储存和干冰运输。我们旨在开发和验证一种新方法，以分析血浆中伊曲康唑、泊沙康唑和伏立康唑的斑点干样点设备（DSSD），并通过 HPLC 系统对其进行定量。
使用正己烷/乙酸乙酯和氨溶液从 DSSD 中提取。使用 HPLC-MS 分析样品。通过日内和日间验证测定准确度和精密度。研究了三唑类药物在 DSSD 上的血浆斑点的稳定性，在室温下放置 1 个月。该方法与验证的 HPLC 标准方法进行了比较，用于定量人血浆中的三唑类药物。
所有化合物的日内和日间准确度和精密度均<15%。三唑类药物在室温下 2 周内稳定。该方法在 0.031-8 mg/L 范围内（伊曲康唑和泊沙康唑）和 0.058-15 mg/L 范围内（伏立康唑）呈线性（r²>0.999）。灵敏度高，检测限分别为 0.008、0.004 和 0.007 mg/L 伊曲康唑、泊沙康唑和伏立康唑。DSSD 方法与标准分析方法之间具有高度相关性（r²>0.94）。
我们开发和验证的用于定量 DSSD 上人类血浆中三唑类药物的方法准确且精确。它克服了与血浆样本储存和运输相关的问题，允许以更经济、更安全的方式进行 TDM。
