HPLC法测定人血浆中伏立康唑的浓度

史长城 叶健 卓广超 楼江 李晴宇 林能明

中图分类号 R927.2 文献标志码 A 文章编号 1001-0408（2021）20-2525-05

DOI 10.6039/j.issn.1001-0408.2021.20.15

摘 要 目的：建立测定人血浆中伏立康唑浓度的方法。方法：血浆经乙腈沉淀蛋白后，以利鲁唑为内标，采用高效液相色谱（HPLC）法测定其中伏立康唑的血药浓度。色谱柱为Agilent Zorbax Eclipse Plus C18，流動相为乙腈-0.01 mol/L磷酸二氢钾溶液（38 ∶ 62，V/V），流速为1.0 mL/min，柱温为40 ℃，检测波长为255 nm，进样量为20 μL。同时将该方法应用于10例使用伏立康唑患者的血药浓度测定。结果：伏立康唑检测质量浓度的线性范围为0.2～20.0 μg/mL（r=0.999 6），定量下限为0.2 μg/mL，日内、日间RSD均小于7%（n=6或n=18），准确度平均值为98.59%～106.18%，提取回收率平均值为86.77%～89.86%（RSD<4%，n=6），稳定性试验实测结果与理论值的偏差在±15%内。10例患者伏立康唑的血药浓度为0.34～5.04 μg/mL。结论：本研究成功建立了快速、高效测定人血浆中伏立康唑浓度的HPLC法。

关键词 伏立康唑;高效液相色谱法;血药浓度

Determination of Voriconazole Concentration in Human Plasma by HPLC

SHI Changcheng1，2，YE Jian3，ZHUO Guangchao4，LOU Jiang1，2，LI Qingyu2，LIN Nengming1，2（1. Zhejiang Provincial Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research， the Affiliated Hangzhou First Peoples Hospital， School of Medicine， Zhejiang University， Hangzhou 310006， China; 2. Dept. of Pharmacy， the Affiliated Hangzhou First Peoples Hospital， School of Medicine， Zhejiang University， Hangzhou 310006， China; 3. Dept. of Respiratory Medicine， the Affiliated Hangzhou First Peoples Hospital， School of Medicine， Zhejiang University， Hangzhou 310006， China; 4. Central Laboratory， the Affiliated Hangzhou First Peoples Hospital， School of Medicine， Zhejiang University， Hangzhou 310006， China）

ABSTRACT   OBJECTIVE： To establish the method for the determination of voriconazole concentration in human plasma. METHODS： After protein precipitation with acetonitrile， using riluzole as internal standard， plasma concentration of voriconazole were determined by HPLC method. The determination was performed on Agilent Zorbax Eclipse Plus C18 column with mobile phase consisted of acetonitrile-0.01 mol/L monopotassium phosphate solution （38 ∶ 62， V/V） at the flow rate of 1.0 mL/min. The column temperature was maintained at 40 ℃， and the detection wavelength was 255 nm. The sample size was 20 μL. Meanwhile， the method was applied to determine plasma concentration of voriconazole in 10 patients receiving voriconazole. RESULTS： The liner range of voriconazole was 0.2-20.0 μg/mL （r=0.999 6）. The lower limit of quantitation was 0.2 μg/mL. RSDs of intra-day and inter-day were both lower than 7% （n=6 or n=18）. Average accuracies were 98.59%-106.18%. Average extraction recoveries were 86.77%-89.86% （RSD<4%，n=6）， and the deviations of measured results and theoretical values of stability tests were within  ±15%. The plasma concentrations of voriconazole in 10 patients were 0.34-5.04 μg/mL. CONCLUSIONS： The study successfully establish a rapid and efficient HPLC method for the determination of voriconazole in human plasma.