人血浆中伏立康唑、伊曲康唑和泊沙康唑的含量测定及其方法学  

Determination of Voriconazole,Itraconazole and Posaconazole in Human Plasma by UPLC-MS/MS and Their Methodology

作　　者：杨叶舟 屈昱晨 苏存锦[1] 潘杰[1] 施爱明[1] YANG Ye-zhou;QU Yu-chen;SU Cun-jin;PAN Jie;SHI Ai-ming(Department of Pharmacy,The No.2 Hospital Affiliated to Soochow University,Suzhou Jiangsu 215004,China)

机构地区：[1]苏州大学附属第二医院药剂科,江苏苏州215004

出　　处：《抗感染药学》2020年第12期1717-1721,共5页Anti-infection Pharmacy

基　　金：苏州市科技局民生科技项目(编号:SYS2019058)。

摘　　要：目的:建立人血浆中伏立康唑、伊曲康唑和泊沙康唑浓度的超高效液相色谱-串联质谱法(UPLC-MS/MS)同时测定方法,并考察了其方法学。方法:采用Thermo Hypersil GOLD(100 mm×2.1 mm,3μm)为色谱柱,水(含0.1%甲酸及10 mmol/L乙酸铵)-甲醇为流动相,梯度洗脱,流速为300μL/min,进样量为2μL,以卡马西平为内标,采用可加热电喷雾离子源(HESI),以单离子检测扫描模式(SIM)进行正离子扫描,采用超高效液相色谱-串联质谱法测定其人血浆中伏立康唑、伊曲康唑和泊沙康唑的浓度。结果:血浆中伏立康唑、伊曲康唑和泊沙康唑浓度在0.20~12.80μg/mL范围内呈现良好的线性关系,得标准曲线方程分别为A伏=1.56×10^(-3)ρ+6.39×10^(-4)(r^(2)=0.9960)、A伊=1.78×10^(-3)ρ+4.17×10^(-4)(r^(2)=0.9966)和A泊=1.46×10^(-3ρ)+7.25×10^(-5)(r^(2)=0.9977),最低定量下限为0.20μg/mL;日内和日间精密度RSD均小于15%,低、中、高浓度质控样本提取回收率均在90.77%~96.99%范围内,测得伏立康唑平均质量浓度为3.90μg/mL。结论:该方法样本处理简便,灵敏度高,专属性强,适用于人血浆中伏立康唑、伊曲康唑和泊沙康唑的血药浓度测定。Objective:To establish an UPLC-MS/MS method for simultaneous determination of voriconazole,itraconazole and posaconazole in human plasma and to study its methodology.Methods:Using Thermo Hypersil GOLD(100 mm × 2.1 mm,3μm)for chromatographic column,water(containing 0.1%formic acid and tendency for 10 L ammonium acetate)-methanol as mobile phase,gradient elution and velocity was 300μL/min,sample quantity wasμL,carbamazepine as internal standard,using heated electrospray ion source(HESI),in a single scanning ion detection model(SIM)positive ion scanning.The concentrations of voriconazole,itraconazole and posaconazole in human plasma were determined by HPLC-TANDEM mass spectrometry.Results:Av=1.56×10^(-3)ρ+6.39×10^(-4)(r^2=0.9960),AI=1.78×10^(-3)ρ+4.17×10^(-4)(r^(2)=0.9966)and AP=1.46×10^(-3)ρ+7.25×10^(-5)(r^(2)=0.9977)showed a good linear relationship with the plasma concentrations of voriconazole and itraconazole in the range of 0.20 g/mL.The average mass concentration of voriconazole was 3.90 g/mL,and the recoveries of low,medium and high concentration samples were between the range of 90.77%and 96.99%.Conclusion:The method is simple,sensitive and specific,and suitable for the determination of blood concentration of voliconazole,itraconazole and posaconazole in human plasma.

关 键 词：伏立康唑 伊曲康唑 泊沙康唑 超高效液相色谱-串联质谱法 UPLC-MS/MS 治疗药物监测 

分 类 号：TQ460.72[医药卫生—药物分析学]