目的：建立测定人血浆中伏立康唑浓度的方法，并应用于临床。方法：采用超高效液相色谱-串联质谱法测定。以酮康唑为内标，色谱柱为Shim-pack VP-ODS，流动相为水（含1‰甲酸及2 mmol/L乙酸铵）-乙腈，梯度洗脱，流速为0.3 ml/min，柱温为40℃；采用电喷雾离子源，以多反应监测方式进行正离子扫描，用于定量分析的离子对分别为m/z 351.2→282.2（伏立康唑）、m/z 532.1→490.2（内标）。结果：伏立康唑血药浓度在1～10000 ng/ml范围内线性关系良好（r＝0.9995，n＝5），定量下限为1 ng/ml；日内、日间RSD＜10％；方法回收率＞90％（RSD＜8％），提取回收率＞70％（RSD＜8％）。采用该法检测10例深部真菌感染患者体内伏立康唑的血药浓度为507.33～7011.24 ng/ml，有3例患者的血药浓度不在推荐治疗浓度范围内。结论：该方法快速、准确、灵敏度高，适用于伏立康唑治疗药物监测。%OBJECTIVE:To develop a method for concentration determination of voriconazole in human plasma and apply it in the clinic. METHODS:UPLC-MS/MS method was adopted. Using ketoconazole as internal standard,the determination was per-formed on Shim-pack VP-ODS column with mobile phase consisted of water(containing 1‰ formic acid and 2 mmol/L ammonium acetate)-acetonitrile(gradient elution)at flow rate of 0.3 ml/min and column temperature of 40℃.The electrospray ion source,pos-itive ionizing pattern and multiple reaction monitoring were used;the mass transition ion-pairs of voriconazole and internal standard were m/z 351.2→282.2 and m/z 532.1→490.2. RESULTS:The linear range of voriconazole were 1-10 000 ng/ml (r=0.999 5,n=5),and the limit of quantitation was 1 ng/ml;RSDs of inter-day and intra-day were all lower than 10%;method recovery was higher than 90%(RSD<8%),and extraction recovery was higher than 70%(RSD<8%). The plasma concentrations of voriconazole in 10 patients with invasive fungal infection determined by this method were 507.33-7 011.24 ng/ml,and those of 3 patients were outside the recommended treatment concentration range. CONCLUSIONS:The established method is fast,accurate and sensitive,and can be applied for the therapeutic drug monitoring of voriconazole.
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