用UPLC-MS/MS法测定重症感染患者血浆中艾沙康唑浓度  

UPLC-MS/MS method for the determination of isavuconazole concentration in plasma of patients with severe infection

作　　者：刘潇阳 李博 陈文倩[1] 陈玥 李朋梅[1] LIU Xiao-yang;LI Bo;CHEN Wen-qian;CHEN Yue;LI Peng-mei(Department of Pharmacy,China-Japan Friendship Hospital,Beijing 100029,China;Department of Pharmacy Administration and Clinical Pharmacy School of Pharmaceutical Sciences,P1eking University,Beijing 100191,China)

机构地区：[1]中日友好医院药学部,北京100029 [2]北京大学药学院临床药学与药事管理学系,北京100191

出　　处：《中国临床药理学杂志》2024年第10期1512-1516,共5页The Chinese Journal of Clinical Pharmacology

基　　金：中日友好医院高水平医院临床业务费专项临床研究基金资助项目(2023-NHLHCRF-YYPP-TS-03)。

摘　　要：目的建立并验证超高效液相色谱-质谱联用法检测人血浆中艾沙康唑的方法,将其应用于血药浓度监测优化药物治疗方案。方法血浆样品经乙腈沉淀蛋白后,以艾沙康唑-D4为内标,色谱柱ACQUITY UPLC BEH C18(2.1 mm×50 mm,1.7μm),2 mmol·L^(-1)乙酸铵-水(含0.1%甲酸)为A相,乙腈(含0.1%甲酸)为B相,流速为0.2 mL·min^(-1),柱温40℃;进样量1μL,用电喷雾离子源正离子模式,多反应监测模式扫描,定量分析离子对分别为m/z 438.30→224.15(艾沙康唑),m/z 442.10→224.10(艾沙康唑-D_(4))。结果艾沙康唑在0.31~40.00μg·mL^(-1)线性关系良好(R2=0.9994),定量下限为0.31μg·mL^(-1),批内和批间精密度分别为2.03%~12.97%和6.05%~10.52%,批内和批间准确度分别在89.82%~110.72%和95.45%~100.13%,低、中、高质量浓度的提取回收率在94.31%~100.23%。该方法测定的14例临床使用艾沙康唑患者的血药浓度结果表明,所有患者均达到艾沙康唑的有效治疗浓度(>1~2μg·mL^(-1))。结论该方法快捷、灵敏、准确、稳定,适用于临床艾沙康唑的血药浓度监测,为治疗方案调整提供技术指导。Objective To establish and validate a method for the detection of isavuconazole in human plasma by ultra-performance liquid chromatography-mass spectrometry,and apply to blood concentration monitoring to optimize drug treatment regimens.Methods The proteins in plasma samples were precipitated with acetonitrile;isavuconazole-D4 was used as the internal standard.Chromatographic column was ACQUITY UPLC BEH C18(2.1 mm×50 mm,1.7μm),flow phase was 2 mmol·L^(-1)ammonium acetate-water(containing 0.1%formic acid,A),acetonitrile(containing 0.1%formic acid,B),flow rate was 0.2 mL·min^(-1),and the column temperature was 40℃.Injection volume was 1μL.The ion pairs were quantitatively analyzed by electro-spray ionization positive ion mode and multiple reaction monitoring,m/z 438.30→224.15(isavuconazole),m/z 442.10→224.10(isavuconazole-D_(4)).Results The linear range of isavuconazole was 0.31 to 40.00μg·mL^(-1)(R²=0.9994);lower limit of quantification(LLOQ)was O.31μg·mL^(-1).The intra-day and inter-day precision ranged from 2.03%to 12.97%and 4.32%to 9.63%,the accuracy deviation ranged from 89.82%to 110.72%and 95.45%to 100.13%,the extraction recovery rates of low,medium and high concentrations ranged from 94.31%to 100.23%.The results of the blood concentrations of 14 patients with clinical use of isavuconazole measured by this method showed that all patients achieved the effective therapeutic concentration of isavuconazole(>1-2μg·mL^(-1)).Conclusion This method is fast,sensitive,accurate and stable,It is suitable for detecting the blood concentration of clinical isavuconazole and providing technical guidance for the adjustment of treatment regimen.

关 键 词：艾沙康唑 超高效液相色谱-质谱联用法 治疗药物监测 唑类抗真菌药 

分 类 号：R978.5[医药卫生—药品]