HPLC-MS/MS法测定人血浆中伏立康唑浓度  

Concentration determination of voriconazole in human plasma by HPLC-MS/MS

作　　者：刘洋[1,2] 邱婷婷[1] 张弨[1] LIU Yang;QIU Ting - ting;ZHANG Chao(Department of Pharmacy, Peking University Third Hospital, Beijing 100191, China;Department of Pharnmcy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China)

机构地区：[1]北京大学第三医院药剂科,北京100191 [2]北京大学药学院药事管理与临床药学系,北京100191

出　　处：《中国临床药理学杂志》2018年第10期1222-1225,共4页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金青年科学基金资助项目(81403009)

摘　　要：目的建立测定人血浆中伏立康唑浓度的方法,并应用于临床样本测定。方法用高效液相色谱-串联质谱法测定。用三氘代伏立康唑同位素内标,色谱柱为Agilent Eclipse Plus C18,流动相为乙腈-0.01 mol·L^(-1)甲酸胺溶液(55∶45),流速为0.3 m L·min^(-1),柱温为40℃;用电喷雾离子源,以多重反应监测方式进行正离子扫描,用于定量分析的离子对分别为m/z 350.2→m/z 281.1(伏立康唑)、m/z 353.2→m/z 284.1(内标)。结果伏立康唑血药浓度在50~1.0×10~4ng·m L^(-1)线性关系良好(r=0.999 7),定量下限为50 ng·m L^(-1);日内、日间精密度RSD均<5%;方法回收率>95%,提取回收率>85%。用该法检测17例使用伏立康唑治疗的血液肿瘤患者的稳态谷浓度,范围为0.38~8.10μg·m L^(-1),有3例患者的血药浓度不在推荐治疗浓度范围内。结论该方法快速、准确、灵敏度高,适用于伏立康唑治疗药物监测。Objective To develop a method for concentration determination of voriconazole in human plasma in order to apply to clinics.Methods HPLC-MS/MS method was adopted. Using d3-voriconazole as internal standard,the determination was performed on Agilent Eclipse Plus C18 column with mobile phase consisted of acetonitrile-water(containing 0. 01 mol·L-1 ammonium formate） 55∶ 45 at flow rate of 0. 3 m L·min-1 and column temperature of 40 ℃. The electrospray ion source,positive ionizing pattern and multiple reaction monitoring were used; the mass transition ion-pairs of voriconazole and internal standard were m/z 350. 2 →m/z 281. 1 and m/z 353. 2 → m/z 284. 1. Results The linear standard concentration range of voriconazole was 50-1. 0 ×104 ng·m L-1(r = 0. 9997）,and the lower limit of quantitation was 50 ng·m L-1. Precision(RSD） of inter-day and intra-day were lower than 5%. Method recovery was higher than 95%,and extraction recovery was higher than 85%. The steady state trough voriconazole plasma concentrations of 17 patients with hematologic malignancy were 0. 38-8. 10μg·m L-1 determined by this method,of which 3 patients were outside of the recommended range. Conclusion The established assay method in this study is rapid,accurate and sensitive,and can be applied for the therapeutic drug monitoring of voriconazole.

关 键 词：伏立康唑 高效液相色谱-串联质谱法 血药浓度 治疗药物监测 

分 类 号：R978.1[医药卫生—药品]