| 用UPLC-MS/MS法测定肝功能不全患者血浆中伏立康唑的浓度 |
| 投稿时间：2020-08-06 修订日期：2020-11-03 点此下载全文 |
| 引用本文：刘琳琳,宋洪涛,严佳.用UPLC-MS/MS法测定肝功能不全患者血浆中伏立康唑的浓度[J].药学实践杂志,2021,39(2):160~163 |
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| 基金项目:中国药理学会课题[CTDM（XM-2017-01-001-29）] |
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| 中文摘要:目的 建立超高效液相色谱-串联质谱（UPLC-MS/MS）方法以测定人血浆中伏立康唑的浓度，用于临床治疗药物监测。方法 血浆中加入甲醇进行蛋白沉淀，取上清液用于UPLC-MS/MS分析。分析柱为InertSustain C18 HP (3.0 mm×100 mm，3 μm)，流动相为水-乙腈（15:85）等度洗脱，流速0.3 ml/min，柱温35 ℃。电喷雾离子化电离源ESI正离子检测，MRM扫描，检测离子分别为m/z：350.9/282.2（伏立康唑）和m/z：307.0/238.0（内标氟康唑）。结果 伏立康唑的血药浓度在0.1～20 μg/ml 范围内线性关系良好（r=0.999 5），方法定量下限为0.1 μg/ml。提取回收率在90%以上，高、中、低3种浓度的日内和日间RSD均<10%。应用所建方法对10例肝功能不全的用药患者进行治疗药物监测，浓度范围在0.97～18.70 μg/ml之间。结论 该方法准确、快速且灵敏度高，适用于临床伏立康唑的治疗药物监测，并为肝功能不全患者的合理化用药提供依据。 |
| 中文关键词:超高效液相色谱-串联质谱 伏立康唑 肝功能不全 治疗药物监测 |
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| The assay of voriconazole in plasma from patients with hepatic insufficiency by UPLC-MS/MS |
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| Abstract:Objective To establish an UPLC-MS/MS method of voriconazole assay in human plasma for clinical therapeutic drug monitoring.Methods The plasma samples were treated with methanol to precipitate protein and the supernatants were assayed by UPLC-MS/MS. The chromatographic column was InertSustain C18 HP (3.0 mm×100 mm, 3 μm) with the mobile phase of water and acetonitrile solution (15:85) at 35 ℃ and 0.3 ml/min flow rate. ESI was used for Mass Spectrum in positive ion MRM mode with target ions m/z: 350.9/282.2(voriconazole) and m/z: 307.0/238.0(fluconazole).Results The linear range of voriconazole was 0.1–20 μg/ml (r=0.999 5）. The lower limit of quantitation was 0.1 μg/ml. The extraction recovery was higher than 90%. RSDs of inter-day and intra-day were all lower than 10%. The plasma concentrations measured by this method were in the range of 0.97 to 18.7 μg/ml from 10 patients with hepatic insufficiency who were treated with voriconazole.Conclusion The established method was fast, accurate and sensitive。It can be applied for the therapeutic drug monitoring of voriconazole，and provided a good base for rationalized medication treatment in patients with hepatic insufficiency. |
| keywords:UPLC-MS/MS voriconazole hepatic insufficiency therapeutic drug monitoring |
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