HPLC测定艾沙康唑血浆药物浓度及其临床应用  

Determination of isavuconazole concentration in human plasma by high-performance liquid chromatography and its clinical application

作　　者：倪伟建 时华飞 袁斯明 聂旋 张圣雨 唐丽琴 NI Weijian;SHI Huafei;YUAN Siming;NIE Xuan;ZHANG Shengyu;TANG Liqin(Department of Pharmacy,The First Affiliated Hospital of USTC(Anhui Provincial Hospital),Division of Life Sciences&Medicine,University of Science&Technology of China,Anhui Hefei 230001,China;School of Pharmacy,Anhui Medical University,Anhui Hefei 230032,China)

机构地区：[1]中国科学技术大学附属第一医院(安徽省立医院)药学部,安徽合肥230001 [2]安徽医科大学药学院,安徽合肥230032

出　　处：《中国医院药学杂志》2024年第18期2129-2134,共6页Chinese Journal of Hospital Pharmacy

基　　金：国家自然科学基金项目(编号:81803602);合肥综合性国家科学中心大健康研究院先导医学与前沿技术研究所科研项目(编号:2023IHM02003)。

摘　　要：目的:建立测定人血浆中艾沙康唑药物浓度的高效液相色谱法(HPLC),为侵袭性霉菌感染患者临床治疗中艾沙康唑的合理使用提供科学依据。方法:采用甲醇沉淀蛋白,Thermo Scientific液相色谱分离系统Ulti Mate 3000,色谱柱为Hypersil ODS2(250 mm×4.6 mm,5μm),流动相为乙腈-乙酸铵(10 mmol·L^(–1))(55∶45,V/V),柱温25℃,流速1 m L·min^(–1),检测波长285 nm,进样量70μL。结果:基于HPLC建立的艾沙康唑血浆浓度测定方法专属性强,在0.20~20.00μg·m L^(–1)血浆浓度范围内线性良好(r=0.9999),回收率为94.09%~102.36%,日内、日间RSD均<5%,室温、4℃与–20℃放置不同时间稳定性均表现良好。临床监测中,1例应用艾沙康唑治疗的患者血药浓度从0.79μg·m L^(–1)调整至1.89μg·m L^(–1)后显示出满意的治疗效果。结论:本研究建立了一种稳定、简便与高效测定患者血浆中艾沙康唑浓度的HPLC分析方法。根据监测结果对患者给药方案进行调整,有助于临床安全、有效与合理用药。OBJECTIVE To develop a method of high-performance liquid chromatography(HPLC)for determining the concentration of isavuconazole in human plasma and to provide a scientific basis for rational dosing of isavuconazole for clinical treatment of invasive mold infection.METHODS Protein was precipitated by acetonitrile on a Thermo HPLC separation system(Ulti Mate 3000)with a Hypersil ODS2(250 mm×4.6 mm,5μm).Mobile phase was composed of acetonitrile-ammonium acetate(10 mmol·L^(–1))(55∶45,V/V)at a flow rate of 1 m L·min^(–1)and a detection wavelength of 285 nm at 25℃.RESULTS The method was developed based upon HPLC.It exhibited high specificity and decent linearity(r=0.9999)within a range of0.20-20.00μg·m L^(–1).Recovery ranged from 94.09%to 102.36%,intra/inter-day RSDs of<5%,decent stability at room temperature,4℃and–20℃respectively for different time periods.One patient on isavuconazole therapy showed a better therapeutic effect after plasma concentration was adjusted from 0.79 to 1.89μg·m L^(–1).CONCLUSION A rapid,stable and efficient HPLC method for determining drug concentration of isavuconazole in human plasma has been successfully established.Based upon the results of therapeutic drug monitoring(TDM),isavuconazole dosing protocol may be adjusted.It contributes to the safety,efficacy and rationalization of its clinical use.

关 键 词：艾沙康唑 血浆药物浓度 高效液相色谱 治疗药物监测 药学监护 

分 类 号：R969[医药卫生—药理学]