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Development and validation of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of voriconazole in human cerebrospinal fluid
Analytical Methods ( IF 2.7 ) Pub Date : 2021-09-08 , DOI: 10.1039/d1ay01103k Liuhan Dong 1, 2 , Nan Bai 1 , Tianlin Wang 3 , Yun Cai 1
Analytical Methods ( IF 2.7 ) Pub Date : 2021-09-08 , DOI: 10.1039/d1ay01103k Liuhan Dong 1, 2 , Nan Bai 1 , Tianlin Wang 3 , Yun Cai 1
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Background: A liquid chromatography-tandem mass spectrometry (LC-MS/MS). Method: For the quantification of voriconazole in human cerebrospinal fluid (CSF) was developed and validated, to guide the clinical use of voriconazole in the treatment of central nervous system infections. CSF samples were treated by protein precipitation with methanol containing fluconazole as the internal standard (IS). The supernatant was analyzed by LC-MS/MS using an Agilent EclipsePlus C18 column eluted with a methanol and water mobile phase at a flow rate of 0.4 mL min−1. Quantification was performed by multiple-reaction monitoring using the precursor and product ion pair 350/280.9 for voriconazole and 307/219.9 for fluconazole. Results: The calibration curve was linear over the range of 0.1–10.0 μg mL−1 (R2 = 0.9991). The inter-day and intra-day precisions were <4.20% and <9.97%, respectively. The recoveries for the three concentrations (0.2, 1.0, and 8.0 μg mL−1) were 99.96%, 107.00%, and 99.85%, and the matrix effects were 99.35%, 103.41%, and 99.64%, respectively. The stability under various conditions was also acceptable. The study also demonstrated that the CSF matrix could be replaced by plasma and artificial CSF. Conclusion: A simple and accurate method for the determination of voriconazole concentrations in human CSF was developed and validated, which can be used for drug monitoring in the treatment of central nervous system infections.
中文翻译：
开发和验证用于定量人脑脊液中伏立康唑的液相色谱-串联质谱 (LC-MS/MS) 方法
背景：液相色谱-串联质谱（LC-MS/MS）。方法：开发并验证了人脑脊液（CSF）中伏立康唑的定量，以指导伏立康唑在中枢神经系统感染治疗中的临床应用。用含有氟康唑的甲醇作为内标 (IS) 通过蛋白质沉淀处理脑脊液样品。使用 Agilent EclipsePlus C18 色谱柱通过 LC-MS/MS 分析上清液，用甲醇和水流动相以 0.4 mL min -1的流速洗脱。使用伏立康唑的前体和产物离子对 350/280.9 和氟康唑的 307/219.9 通过多反应监测进行定量。结果s：校准曲线在 0.1–10.0 μg mL -1范围内呈线性（R 2 = 0.9991）。日间和日内精密度分别为 <4.20% 和 <9.97%。三种浓度（0.2、1.0 和 8.0 μg mL -1）的回收率分别为 99.96%、107.00% 和 99.85%，基质效应分别为 99.35%、103.41% 和 99.64%。在各种条件下的稳定性也是可以接受的。该研究还表明，可以用血浆和人工脑脊液代替脑脊液基质。结论: 建立并验证了一种简便、准确的测定人脑脊液中伏立康唑浓度的方法，可用于中枢神经系统感染治疗中的药物监测。
更新日期：2021-09-17
中文翻译：
开发和验证用于定量人脑脊液中伏立康唑的液相色谱-串联质谱 (LC-MS/MS) 方法
背景：液相色谱-串联质谱（LC-MS/MS）。方法：开发并验证了人脑脊液（CSF）中伏立康唑的定量，以指导伏立康唑在中枢神经系统感染治疗中的临床应用。用含有氟康唑的甲醇作为内标 (IS) 通过蛋白质沉淀处理脑脊液样品。使用 Agilent EclipsePlus C18 色谱柱通过 LC-MS/MS 分析上清液，用甲醇和水流动相以 0.4 mL min -1的流速洗脱。使用伏立康唑的前体和产物离子对 350/280.9 和氟康唑的 307/219.9 通过多反应监测进行定量。结果s：校准曲线在 0.1–10.0 μg mL -1范围内呈线性（R 2 = 0.9991）。日间和日内精密度分别为 <4.20% 和 <9.97%。三种浓度（0.2、1.0 和 8.0 μg mL -1）的回收率分别为 99.96%、107.00% 和 99.85%，基质效应分别为 99.35%、103.41% 和 99.64%。在各种条件下的稳定性也是可以接受的。该研究还表明，可以用血浆和人工脑脊液代替脑脊液基质。结论: 建立并验证了一种简便、准确的测定人脑脊液中伏立康唑浓度的方法，可用于中枢神经系统感染治疗中的药物监测。
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