高效液相色谱-串联质谱法测定侵袭性真菌感染患者伏立康唑的血药浓度  

Determination of voriconazole plasma concentrations in patients suffering invasive fungi infections by HPLC MS/MS

作　　者：曲彩红[1] 周凤丽[1] 黄建华[1] 谢俊强[1] 

机构地区：[1]中山大学附属第三医院药学部,广东广州510630

出　　处：《中国医院药学杂志》2013年第1期19-23,共5页Chinese Journal of Hospital Pharmacy

基　　金：广东省科技计划项目(编号:2011B030800083);广东省医学科研基金(编号:A2011189)

摘　　要：目的:建立人血浆中伏立康唑浓度的高效液相色谱-串联质谱测定法,初步考察患者体内伏立康唑谷浓度范围。方法:待患者连续用药3 d后于下次给药前抽取患者的静脉血2mL至肝素钠抗凝管中,血浆样品经甲醇沉淀蛋白、离心后直接测定。以酮康唑为内标。液相条件:流动相为乙腈-0.01mol.L-1醋酸铵溶液(90∶10),流速0.3mL.min-1,进样量1.0μL,柱温35℃;质谱条件:离子源为电喷雾(ESI)离子源,正离子电离模式,干燥气(N2)温度350℃,雾化气(N2)压力275.8 kPa,干燥气(N2)流量9.00L.min-1,电喷雾电压4 000 V,扫描方式为多反应监测(MRM)模式。结果:该方法专属性好。伏立康唑质量浓度在0.1～10μg.mL-1范围内线性良好。临床10名患者的血药质量浓度范围在1.04～7.16μg.mL-1之间,个体间差异显著。结论:该方法简单快速,灵敏度高,可用于伏立康唑体内血药浓度检测。临床医师有必要根据伏立康唑血药浓度对患者进行个体化的剂量调整。OBJECTIVE To establish the method for determining the concentration of voriconazole in human plasma by high performance liquid chromatography-tandem mass spectrometry （HPLOMS/MS）, and investigate the range of pateints＇ trough concentration of voriconazole in vivo. METHODS 10 patients＇ venous blood was collected in heparin sodium anticoagulation tubes before the next administration after 3 days of continuous voriconazole medication. Blood plasma samples were processed with methanol to precipitate albumen and were directly determined after being centrifugated. Internal standard was ketoconazole. Liquid phase condition： methyl cyanides-0. 01 mol. L-1 ammonium acetate（90： 10） as mobile phase, flow rate was 11. 3 mL.min -1 , injection volume was 1.0 μL, column temperature： 35℃ ; mass spectral condition： Electrospray Ion Source（ESI） and positive ionizing pattern was used, drying gas （N2） temperature：350 ℃, pulverization pressure： 275.8 kPa, flow rate of drying gas （N2） ： 9. 00 L·min -1, electrospray voltage： 4000 V, scan mode was multiple reaction monitoring（MRM）pattern. RESULTS This method is highly specific. The linearity of voriconazole is good within the limits of 0. 1 - 10μg·mL-1. 10 pa tients＇ plasma concentration of voriconazole was at the range of 1.04- 7. 16μg·mL-1 , interindividual variation was significant. CONCLUSION This methods was simple, fast and sensitive, it can be used to determine the plasma concentration of voricon azole in vivo. There is a need for individual voriconazole dosage modification based on plasma concentrations.

关 键 词：伏立康唑 血药浓度测定 高效液相色谱-串联质谱法 侵袭性真菌感染 

分 类 号：R969.1[医药卫生—药理学]