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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刘琳琳 中国人民解放军联勤保障部队第九〇〇医院药剂科福建 福州 350025  
宋洪涛 中国人民解放军联勤保障部队第九〇〇医院药剂科福建 福州 350025 sohoto@vip.163.com 
严佳 中国人民解放军联勤保障部队第九〇〇医院药剂科福建 福州 350025  
基金项目:中国药理学会课题[CTDM(XM-2017-01-001-29)]
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
 
The assay of voriconazole in plasma from patients with hepatic insufficiency by UPLC-MS/MS
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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