文章摘要
邢亚茹,张丽军,乐晓琴,陈军,尹林,卢洪洲,李迎迎.UPLC-MS法测定艾滋合并结核患者血浆中替诺福韦浓度[J].药学与临床研究,2021,29(2):17~20
UPLC-MS法测定艾滋合并结核患者血浆中替诺福韦浓度
UPLC-MS Determination of Plasma Tenofovir Concentrations in Patients with HIV Coinfecting Tuberculosis
投稿时间:2020-10-09  修订日期:2021-04-13
DOI:
中文关键词: 超高效液相色谱-质谱联用  替诺福韦  艾滋合并结核  血浆
英文关键词: UPLC-MS  Tenofovir  HIV-TB coinfection  Plasma
基金项目:十三五重大新药创制-抗艾滋病病毒新药临床评价技术平台建设项目(2017ZX09304027)
作者单位E-mail
邢亚茹 桂林医学院 xingyaru1203@163.com 
张丽军 上海市公共卫生临床中心  
乐晓琴 上海市公共卫生临床中心  
陈军 上海市公共卫生临床中心  
尹林 上海市公共卫生临床中心  
卢洪洲 上海市公共卫生临床中心  
李迎迎 桂林医学院 liyyl@163.com 
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中文摘要:
      目的:建立血浆中替诺福韦(tenofovir,TFV)含量测定的方法,测定艾滋合并结核患者给药后血浆中替诺福韦的浓度。方法:血浆采用甲醇沉淀蛋白,色谱柱为Kinetex Phenyl-Hexyl(50 mm×3.0 mm,2.6 μm),流动相为5 mmol·L-1甲酸铵溶液(A)-甲醇溶液(B),每个样品分析时间为3.5 min,进样量:10 μL。采用超高效液相色谱串联质谱(UPLC-MS)中的正离子多反应监测模式(MRM)进行检测,TFV和同位素内标(TFV-d7)m/z分别是288.0→176.1,295.3→183.2。该方法用于21例艾滋合并结核患者的血浆标本检测。结果:TFV在1~200 ng·mL-1范围内呈线性关系,定量下限为1 ng·mL-1,日内和日间精密度均<15%,准确度在85%~115%,低、高浓度质控的提取回收率分别为114.36%、112.96%,基质效应89.49%、89.60%。稳定性试验和稀释质控样品实验(稀释因子=5和4)中低、高浓度质控准确度均在85%~115%。21例患者的TFV平均浓度为108.53±87.94(2.02~413) ng·mL-1。患者TFV的浓度有71.4%在线性范围内。结论:该方法简单、快速、灵敏,可用于测定该类患者血浆中TFV的含量。
英文摘要:
      Objective: To develop a method for detecting plasma tenofovir (TFV) concentrations in patients with human immunodeficiency virus (HIV)-tuberculosis (TB) coinfection. Methods: Plasma was protein-precipitated with methanol. The separation was performed on a Kinetex phenyl-hexyl (50 mm × 3.0 mm, 2.6 μm) column with mobile phase consisted of 5 mmol·L-1 ammonium formate solution (A)-methanol solution (B). The sample (10 μL) was loaded to ultra performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) for drug concentration detection under the positive multiple reaction monitoring (MRM) model. The sample detection time was 3.5 min. The m/z of TFV and its internal standard (TFV-d7) were 288.0→176.1 and 295.3→183.2, respectively. The validated UPLC-MS/MS method was used to detect the plasma TFV concentrations in 21 patients with HIV-TB coinfection. Results: TFV concentrations showed a good linear relationship in the range of 1-200 ng·mL-1, with the lower limit of quantification at 1 ng·mL-1. The intraday and intraday precisions were within 15%, with accuracy between 85.00% and 115.00%. The extraction recoveries (ER), and matrix effects (ME) of quality controls with low and high concentrations (LQC and HQC) were 114.36% and 112.96% for ER, and 89.49% and 89.60% for ME, respectively. The accuracies of stability and dilution factors were all between 85% and 115%. For patients with HIV-TB coinfection, 71.4% had plasma TFV concentrations in the range of 1-200 ng·mL-1. Conclusions: The developed UPLC-MS method is simple, rapid and sensitive, and suitable for TFV detection in patients with HIV-TB coinfection.
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