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LC-MS/MS法同时测定人血浆中伏立康唑和替加环素的浓度

Simultaneous determination of voriconazole and tigecycline in human plasma by an LC-MS/MS method

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【作者】 马霖孙加琳李恩泽王辉明张辉曹志红徐文

【Author】 MA Lin;SUN Jia-lin;LI En-ze;WANG Hui-ming;ZHANG Hui;CAO Zhi-hong;XU Wen;Department of Pharmacy,the Affiliated Hospital of Qingdao University;

【通讯作者】 徐文;

【机构】 青岛大学附属医院药学部

【摘要】 目的建立可同时快速测定人血浆中伏立康唑和替加环素质量浓度的方法。方法以甲醇为沉淀剂,经蛋白沉淀法处理,进高效液相串联质谱系统(HPLC-MS/MS)分析,色谱柱:Ultimate AQ-C18 (2. 1 mm×100 mm,3. 0μm),流动相:乙腈-0. 1%甲酸梯度洗脱,流速均为0. 4 m L·min-1,柱温:40℃,进样量:5μL,电喷雾电离,用多反应监测模式,定量分析离子对分别为m/z 350. 1→m/z 281. 3(伏立康唑)、m/z 586. 7→m/z 569. 2(替加环素)、m/z343. 2→m/z 239. 2(三唑仑)。结果伏立康唑标准曲线方程为y=7. 8×10-3x+3. 1×10-4(r=0. 999 3),线性范围为5010000 ng·m L-1;替加环素标准曲线方程为y=1. 6×10-3x+4. 0×10-4(r=0. 999),线性范围为255000ng·m L-1。伏立康唑和替加环素的批间和批内精密度均在6. 48%14. 37%,准确度均在85. 20%107. 08%,平均提取回收率均大于90. 50%,稳定性好。结论本方法样品处理简便,灵敏度高,专属性强,适用于伏立康唑和替加环素的血药浓度监测。

【Abstract】 Objective To develop an LC-MS/MS method for thesimultaneous determination of voriconazole and tigecycline in human plasma. Methods Plasma samples were pretreated by protein precipitation method. The separation was performed using an Ultimate AQ-C18 column( 3. 0 μm,2. 1 × 100 mm) column. Gradient elution was selected using actonitrial and 0. 1% formic acid. The flow rate was 0. 4 ml·min-1,the injection volumn was 5μl,and the electrospray ionization source was used. The multi-reaction monitoring mode was used to quantitatively analyze the ionization pairs as m/z 350. 1 → m/z 281. 3( voriconazole),m/z 586. 7 → m/z 569. 2( tigecycline) 、m/z 343. 2 →m/z 239. 2( triazolam). Results The standard curve of voriconazole was y = 7. 8 × 10-3 x + 3. 1 × 10-4( r = 0. 999 3), the linear range was50 10000 ng·mL-1; The standard curve of tigecycline was y = 1. 6 ×10-3 x + 4. 0 × 10-4( r = 0. 999 1) with a linear range of 25 5000 ng·mL-1. The rest of inter-assay and intra-assay precision were between6. 48% and 14. 37%. The accuracy were between 85. 20% and107. 08%,and average extraction recoveries of two analytes were greater than 90. 50%,and the stability was good. Conclusion The LC-MS/MS method is rapid and accurate,can meet the request of therapeutic drug monitoring of voriconazole and tigecycline.

  • 【文献出处】 中国临床药理学杂志 ,The Chinese Journal of Clinical Pharmacology , 编辑部邮箱 ,2019年24期
  • 【分类号】R969
  • 【被引频次】3
  • 【下载频次】402
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