UPLC-MS/MS法同时测定人血浆中5种抗真菌药物的血药浓度  

Simultaneous determination of 5 antifungal drugs in human plasma by UPLC-MS/MS

作　　者：姚远 卢伟 吕光辉 YAO Yuan;LU Wei;LYU Guang-hui(Department of Pediatrics,Shiyan Taihe Hospital(Affiliated Hospital of Hubei University of Medicine),Shiyan Hubei 442000;Department of Pharmacy,Shiyan Taihe Hospital(Affiliated Hospital of Hubei University of Medicine),Shiyan Hubei 442000)

机构地区：[1]十堰市太和医院(湖北医药学院附属医院)儿科,湖北十堰442000 [2]十堰市太和医院(湖北医药学院附属医院)药学部,湖北十堰442000

出　　处：《中南药学》2021年第8期1590-1594,共5页Central South Pharmacy

摘　　要：目的 建立UPLC-MS/MS法同时测定血浆中5种抗真菌药物(氟康唑、伏立康唑、伊曲康唑、泊沙康唑和卡泊芬净)的浓度,并应用于临床治疗药物监测。方法在50 μL血浆样品中加入内标,甲醇沉淀蛋白后用流动相稀释并进样分析。采用C_(18)色谱柱(2.1 mm×50 mm,1.7 μm),0.1%甲酸水溶液-乙腈溶液为流动相,梯度洗脱,流速为 0.3 mL·min~(-1),柱温为40℃;采用电喷雾离子化源(ESI),正离子多反应监测模式扫描分析。结果氟康唑的线性范围为 0.80~40.0 μg·mL^(-1),其他4种抗真菌药物的线性范围约为0.20~12.00 μg·mL^(-1),r 均大于0.99;各浓度的批内和批间RSD均小于6.8%;提取回收率在 91.06%~106.7%,方法准确度在91.57%~103.4%,基质效应范围为92.17%~103.2%。收集56例临床中侵袭性真菌感染并接受伏立康、氟康唑和卡泊芬净唑治疗的患者,研究结果显示伏立康唑的血药谷浓度在0.54~8.19 μg·mL^(-1),氟康唑血药谷浓度在5.33~15.21 μg·mL^(-1),卡泊芬净血药谷浓度在1.58~9.12 μg·mL^(-1),患者个体差异较大。结论该方法准确可靠,操作简便,重复性好,适用于快速检测人血浆中5种抗真菌药物的血药浓度测定。Objective To simultaneous determine 5 antifungals(fluconazole,voriconazole,itraconazole,posaconazole and caspofungin)in human plasma by UPLC-MS/MS for clinical therapeutic drug monitoring.Methods The serum samples(50μL)were precipitated with methanol after adding the internal standard.The chromatographic separation was performed on C_(18) column(2.1 mm×50 mm,1.7μm)with water(containing 0.1%formic acid)as the mobile phase A and acetonitrile as the mobile phase B.The flow rate was 0.3 mL·min-1.Positive electrospray ionization source was used together with multiple reaction monitoring.Results The linear concentration range of the calibration curves for fluconazole was 0.80~40.0μg·mL^(-1),tand that for other 4 antifungals were 0.20~12.00μg·mL^(-1),with r all higher than 0.99.The RSDs of the precision were less than 6.8%.The average recovery of the 5 antifungals were at 91.06%~106.7%.The accuracy ranged from 91.57%~103.4%.The matrix effect ranged from 92.17%~103.2%.The 56 patients receiving antifungal therapy were collected from ICU,Department of Hemotology,Nephrology and Pneumology.The trough blood concentration of voriconazole,fluconazole and caspofungin ranged 0.54~8.19,5.33~15.21,and 1.58~9.12μg·mL^(-1),respectively.Conclusion The method is accurate,reliable,simple and repeatable,which is suitable for the determination of blood concentrations of 5 antifungals in human plasma.

关 键 词：超高效液相色谱-质谱法 抗真菌药物 血药浓度 

分 类 号：R927[医药卫生—药学]