高效液相色谱法测定人血浆中伏立康唑浓度

目的:建立一种简单高效的高效液相色谱(HPLC)法用来检测人体中伏立康唑的血药浓度,并应用于临床中伏立康唑用药监测,以促进其个体化用药。方法:色谱柱:Kromasil C18(4.6 mm×150 mm,5μm),柱温:35℃,流速:1.0 mL·min^-1,流动相∶甲醇-水(60∶40),检测波长:257 nm,内标:酮康唑。对该方法进行方法学验证。结果:该方法专属性良好,血浆中伏立康唑在0.1~20.0μg·mL^-1范围内线性良好(r=0.999 6),定量下限为0.1μg·mL^-1。高、中、低3个浓度提取回收率分别为(90.68±10.32)%、(92.82±8.26)%、(97.47±4.58)%;日内精密度RSD分别为5.87%、7.85%、4.10%;日间精密度RSD分别为5.64%、3.30%、2.74%。对某院20例(男12例,女8例)使用伏立康唑抗真菌治疗的患者运用该方法进行了监测,结果显示浓度范围在0.71~13.51μg·mL^-1之间。结论:本方法专属性高,操作简便,结果准确,可用于临床上伏立康唑血药浓度的检测,从而促进其个体化用药的推广。

High performance liquid chromatography determination of voriconazole in human plasma

OBJECTIVE To establish a simple and effective high performance liquid chromatography method for the determination of voriconazole in human plasma.This method was used to monitor voriconazole blood concentration and promote the individualized medication. METHODS The analysis was conducted using a Kromasil C₁₈(4.6 mm×150 mm,5 μm)column and the column temperature was 35℃. The mobile phase consisted of methanol and water (60:40). The flow rate was 1 mL·min and the detection was performed at 257 nm. The internal standard substance was ketoconazole. RESULTS The specificity of the method was good. The linearity of voriconazole in plasma was good in the range of 0.1-20.0 μg·mL^-1. The lower limit of quantitation was 0.1 μg·mL^-1. The recovery rates of low, middle and high concentrations were (90.68±10.32)%. (92.82±8.26)%, (97.47±4.58)%, respectively. The intra-day RSDs were 5.87%, 7.85% and 4.10%, and the inter-day RSDs were 5.64%, 3.30% and 2.74%. Twenty patients (12 males and 8 females) treated with voriconazole for antifungal therapy in a hospital were monitored using this method, and the results showed that the concentration ranged between 0.71 and 13.51 μg·mL^-1. CONCLUSION The method is highly specific, simple and accurate, and can be used to detect the plasma concentration of voriconazole in clinical practice so as to promote the individualized medication.