UPLC-MS法测定艾滋合并结核患者血浆中替诺福韦浓度

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,2.6μm),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....

UPLC-MS Determination of Plasma Tenofovir Concentrations in Patients with HIV Coinfecting Tuberculosis

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,2.6μm)column with mobile phase consisted of 5 mmol·L^-1 ammonium formate solution(A)-methanol solution(B).The sample(10μL)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.