HPLC法測定人血漿中伏立康唑的濃度

史長城 葉健 卓廣超 樓江 李晴宇 林能明

中圖分類號 R927.2 文獻標志碼 A 文章編號 1001-0408（2021）20-2525-05

DOI 10.6039/j.issn.1001-0408.2021.20.15

摘 要 目的：建立測定人血漿中伏立康唑濃度的方法。方法：血漿經乙腈沉淀蛋白后，以利魯唑為內標，采用高效液相色譜（HPLC）法測定其中伏立康唑的血藥濃度。色譜柱為Agilent Zorbax Eclipse Plus C18，流動相為乙腈-0.01 mol/L磷酸二氫鉀溶液（38 ∶ 62，V/V），流速為1.0 mL/min，柱溫為40 ℃，檢測波長為255 nm，進樣量為20 μL。同時將該方法應用于10例使用伏立康唑患者的血藥濃度測定。結果：伏立康唑檢測質量濃度的線性范圍為0.2～20.0 μg/mL（r=0.999 6），定量下限為0.2 μg/mL，日內、日間RSD均小于7%（n=6或n=18），準確度平均值為98.59%～106.18%，提取回收率平均值為86.77%～89.86%（RSD<4%，n=6），穩定性試驗實測結果與理論值的偏差在±15%內。10例患者伏立康唑的血藥濃度為0.34～5.04 μg/mL。結論：本研究成功建立了快速、高效測定人血漿中伏立康唑濃度的HPLC法。

關鍵詞 伏立康唑;高效液相色譜法;血藥濃度

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.