HPLC法测定人血浆中伏立康唑及其代谢物的浓度
投稿时间:2018-08-03  修订日期:2018-11-30  点此下载全文
引用本文:王志君,杨云云,张文静,王学彬,宋洪杰,王卓.HPLC法测定人血浆中伏立康唑及其代谢物的浓度[J].药学实践杂志,2019,37(2):162~165
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作者单位E-mail
王志君 海军军医大学附属长海医院药学部, 上海 200433  
杨云云 海军军医大学附属长海医院药学部, 上海 200433  
张文静 海军军医大学附属长海医院药学部, 上海 200433  
王学彬 海军军医大学附属长海医院药学部, 上海 200433  
宋洪杰 海军军医大学附属长海医院药学部, 上海 200433  
王卓 海军军医大学附属长海医院药学部, 上海 200433 wangzhuo088@163.com 
中文摘要:目的 建立一种快速、灵敏、准确、稳定的测定人血浆中伏立康唑及其代谢物浓度的方法,用于伏立康唑临床治疗药物监测。方法 采用高效液相色谱(HPLC)-紫外(UV)检测法,以罂粟碱为内标,乙腈蛋白沉淀法处理血浆样品。色谱柱为ACE5C18-AR (150 mm×4.6 mm),流动相为0.025 mol/L磷酸二氢钠(含三乙胺400 μl/L,用0.25 mol/L的氢氧化钠调至pH=7.0)-乙腈(67:33),流速为l ml/min,柱温为40℃,检测波长为255、276 nm (双波长检测),进样量为20 μl。结果 伏立康唑氮氧化物、伏立康唑和罂粟碱的保留时间分别为4.5、11.3、13.7 min;血浆中伏立康唑、伏立康唑氮氧化物线性范围均为0.5~20.0 μg/ml (r=0.999 5),定量下限均为0.5 μg/ml,批内、批间RSD均<11%,定量下限、低、中、高梯度浓度提取回收率在90.3%~109.9%之间。结论 该方法操作简便,结果准确,适用于伏立康唑的临床治疗药物监测和对其主要代谢物的测定。
中文关键词:伏立康唑  伏立康唑氮氧化物  高效液相色谱  治疗药物监测
 
Determination of voriconazole and its metabolites in human plasma by HPLC
Abstract:Objective To establish a HPLC method for the determination of the voriconazole concentration in human plasma,which can be used for voriconazole monitoring clinically.Methods High performance liquid chromatography (HPLC-UV) detection method was used with papaverine as internal standard.Acetonitrile protein precipitation method was employed to treat plasma samples.The chromatographic column was ACE5C18-AR150 mm×4.6 mm with the mobile phase 0.025 mol/L sodium dihydrogen phosphate (containing triethylamine 400 μl/L,pH=7.0 adjusted by 0.25 mol/L sodium hydroxide) - acetonitrile (67∶33).The flow rate was l ml/min,the column temperature at 40 ℃,the detection wavelength at 255,276 nm (double wavelength detection) and sampling amount 20 μl.Results The retention time of voriconazole nitrogen oxide,voriconazole and papaverine were 4.5,11.3 and 13.7 min respectively.The linear ranges of voriconazole and voriconazole nitrogen oxides in plasma were 0.5-20.0 μg/ml (r=0.999 5).The quantitative lower limits were 0.5 μg/ml with RSD< 11%.The recovery rates of extraction were between 90.3% and 109.9%.Conclusion This simple and accurate method is suitable for clinical monitoring of voriconazole.
keywords:voriconazole  voriconazole nitrogen oxide  HPLC  therapeutic drug monitoring
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