Department of Laboratory Medicine, The First Hospital of Jilin University, Changchun 130061, China.
School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin 124221, China.
Molecules. 2022 Aug 31;27(17):5609. doi: 10.3390/molecules27175609.
The TDM of voriconazole which exhibits wide inter-individual variability is indispensable for treatment in clinic. In this study, a method that high-performance liquid chromatography tandem mass spectrometry cubed (HPLC-MS) is first built and validated to quantify voriconazole in human plasma. The system is composed of Shimadzu Exion LC UPLC coupled with a Qtrap 5500 mass spectrometer. The separation of voriconazole is performed on a Poroshell 120 SB-C18 column at a flow rate of 0.8 mL/min remaining 7 min for each sample. The calibration curves are linear in the concentration range of 0.25-20 μg/mL. Intra-day and inter-day accuracies and precisions are within 8.0% at three concentrations, and the recoveries and matrix effect are all within accepted limits. In terms of stability, there is no significant degradation of voriconazole under various conditions. The HPLC-MS and HPLC-MRM (multiple reaction monitoring) methods are compared in 42 patients with Passing-Bablok regression and Bland-Altman plots, and the results show no significant difference between the two methods. However, HPLC-MS has a higher S/N (signal-to-noise ratio) and response than the MRM. Finally, the HPLC-MS assay is successfully applied to monitor the TDM (therapeutic drug monitoring) of voriconazole in human plasma, and this verifies that the dosing guidelines for voriconazole have been well implemented in the clinic and patients have received excellent treatment.
伏立康唑的治疗药物监测（TDM）具有广泛的个体间变异性，在临床治疗中不可或缺。本研究首次建立并验证了高效液相色谱串联质谱法（HPLC-MS）测定人血浆中伏立康唑的方法。该系统由 Shimadzu Exion LC UPLC 与 Qtrap 5500 质谱仪联用组成。伏立康唑的分离在 Poroshell 120 SB-C18 柱上进行，流速为 0.8 mL/min，每个样品保留 7 min。校准曲线在 0.25-20 μg/mL 的浓度范围内呈线性。在三个浓度下，日内和日间准确度和精密度均在 8.0%以内，回收率和基质效应均在可接受范围内。就稳定性而言，伏立康唑在各种条件下均无明显降解。通过 Passing-Bablok 回归和 Bland-Altman 图比较了 HPLC-MS 和 HPLC-MRM（多重反应监测）方法，结果表明两种方法无显著差异。然而，HPLC-MS 的 S/N（信噪比）和响应均高于 MRM。最后，HPLC-MS 测定法成功应用于监测人血浆中伏立康唑的 TDM（治疗药物监测），这验证了伏立康唑的给药指南在临床上得到了很好的实施，并且患者得到了很好的治疗。
