HPLC内标法测定人血清中伏立康唑的浓度及其应用  

High performance liquid chromatography internal standard method determination of voriconazole in human serum and its application

作　　者：李俊明[1] 覃禹[1] 卓思珺[1] 谢瑞杰[1] 刘代华[1] LI Junming;QIN Yu;ZHUO Si-jun(Liuzhou People’s Hospital,Liuzhou 545006,China)

机构地区：[1]柳州市人民医院,广西柳州545006

出　　处：《中国处方药》2022年第3期22-25,共4页Journal of China Prescription Drug

基　　金：广西壮族自治区卫生和计划生育委员会自筹经费科研课题(Z20180291,Z20170686);柳州市人民医院院内立项课题(lry201604)。

摘　　要：目的建立高效液相色谱(HPLC)内标法监测人血清中伏立康唑(VRC)的浓度,为临床个体化用药提供依据。方法采用10%高氯酸沉淀蛋白法处理人血清样品,以硝西泮为内标,Hypersil ODS柱为色谱柱,25 mmol/L KH_(2)PO_(4)缓冲液∶甲醇∶乙腈(55∶15∶30)为流动相,流速1.0 ml/min,柱温35℃,HPLC-UV检测伏立康唑血药浓度。结果伏立康唑与内标色谱峰分离良好,无内源性物质峰干扰,在血药浓度0.3~12μg/ml范围内线性关系良好,r=0.9997(n=6)。定量下限为0.3μg/ml,高、中、低三个浓度提取回收率分别为(96.35±1.70)%、(102.44±3.52)%、(97.34±2.39)%,日内精密度RSD分别为4.39%、4.74%、2.90%;日间精密度RSD分别为6.5%、6.0%、4.8%;使用该方法检测自2016年6月~2020年2月的2963份样本,其中624份(21.06%)不在治疗窗内。结论本检测方法准确灵敏、快速便捷,适用于临床伏立康唑血药浓度监测。伏立康唑血药浓度个体差异大,临床应进行治疗药物浓度监测以指导个体化用药。Objective To establish a HPLC method for the determination of voriconazole in human serum and used to monitor VRC blood concentration to promote the individualized medication.Methods Serum samples were spiked with nitrazepam and then treated with 10% HClO_(4) for protein precipitation.The analysis was conducted using Hypersil ODS column and the column temperature was 35℃.The mobile phase consisted of 25 mmol/L KH_(2)PO_(4) buffer solution and methanol and acetonitrile(55∶15∶30).The flow rate was 1.0 ml/min and the detection was performed at 256 nm.Results The specificity of the method was good.The linearity of concentration of voriconazole was good in the range of 0.3~12μg/ml,r=0.9997(n=6).The lower limit of quantitation was 0.3μg/ml.The recoveries of high,medium and low concentrations were(96.35±1.70)%,(102.44±3.52)%,and(97.34±2.39)%respectively.The intra-day precision RSD were 4.39%,4.74%,2.90% respectively.The daily precision RSD were 6.5%,6.0% and 4.8% respectively.2963 samples were tested in our hospital from June 2016 to February 2020 using this method.The 624(21.06%)concentration were not within the target range.Conclusion The established method is accurate,sensitive,rapid and suitable for the determination of human serum VRC concentration.Blood concentration of voriconazole varies greatly among individuals.Therapeutic drug monitoring can be used to guide individual medication.

关 键 词：伏立康唑 高效液相色谱法 内标法 血药浓度 个体化用药 

分 类 号：R927.2[医药卫生—药学]