二维液相色谱法测定人血浆中泊沙康唑药物浓度及其在儿科临床的应用  

Determination of posaconazole in the plasma by two-dimensional liquid chromatography and its application in pediatric patients

作　　者：张胜男 周宇雪[1] 王丹姝 吕萌 ZHANG Sheng-nan;ZHOU Yu-xue;WANG Dan-shu;LYU Meng(Department of Pharmacy,Children’s Hospital Affiliated to Zhengzhou University,Zhengzhou 450000)

机构地区：[1]郑州大学附属儿童医院药学部,郑州450000

出　　处：《中南药学》2023年第1期249-252,共4页Central South Pharmacy

基　　金：河南省重点研发与推广专项(科技攻关)(No.212102310445)。

摘　　要：目的建立一种测定血浆中泊沙康唑的二维液相色谱方法,并应用于临床检测。方法全血经过离心、去蛋白前处理后进样分析,通过一维液相色谱柱Aston SX1(3.5 mm×25 mm,5μm)对泊沙康唑进行初步萃取分离,由中间柱Aston SCB(4.6 mm×125 mm,5μm)转移至二维液相色谱柱Aston SCB(4.6 mm×10 mm,3.5μm)进行最终的分离分析。一维流动相为甲醇-乙腈-磷酸铵盐水溶液=1∶3∶3(V/V/V,氨水调pH至7.00),流速0.7 mL·min^(-1);二维液相色谱系统流动相为25 mmol·L^(-1)磷酸铵盐水溶液-1.0 mmol·L^(-1)磷酸氢二铵溶液-乙腈=18∶22∶60,流速1.0 mL·min^(-1)。柱温40℃,紫外检测波长262 nm,进样量200μL。结果泊沙康唑与血浆中其他杂质分离良好,质量浓度在0.042~3.04 mg·L^(-1)与峰面积呈良好的线性关系(r=0.9993),平均回收率为100.74%。结论本法准确可靠,适用于临床开展常规泊沙康唑血药浓度监测及药动学研究。Objective To establish a detection method by using the two-dimensional liquid chromatography to determine the concentration of posaconazole in the plasma.Methods After centrifugation and protein precipitation,the samples were analyzed.The initial extraction and separation of posaconazole were performed on a one-dimensional liquid chromatographic column Aston SX1(3.5 mm×25 mm,5μm),and subsequently transferred to Aston SCB(4.6 mm×125 mm,5μm)for the final separation and analysis by the intermediate column Aston SCB(4.6 mm×10 mm,3.5μm).The one-dimensional mobile phase was methyl-acetonitrile-ammonium phosphate aqueous solution(1∶3∶3,V/V/V,with pH being adjusted to 7.00 by ammonium hydroxide)with a flow rate of 0.7 mL·min^(-1).The two-dimensional mobile phase was a mixed system of 25 mmol·L^(-1)ammonium phosphate aqueous solution-1.0 mmol·L^(-1)diammonium hydrogen phosphate solutionacetonitrile(18∶22∶60).The flow rate was 1.0 mL·min^(-1).The column temperature was 40℃,the wavelength was 262 nm and the injection volume was 200μL.Results Posaconazole was well separated from other impurities in the plasma.The plasma concentration of posaconazole had a good linear relationship with their peak areas at 0.042-3.04 mg·L^(-1)(r=0.9993).The average recovery was 100.74%.Conclusion The method is sensitive and accurate,which is suitable for the routine determination and pharmacokinetic study of posaconazole.

关 键 词：二维液相色谱 泊沙康唑 药物浓度 测定 临床应用 

分 类 号：R969[医药卫生—药理学]