Rapid quantification of tenofovir in umbilical cord plasma and amniotic fluid in hepatitis B mono-infected pregnant women during labor by ultra-performance liquid chromatography/tandem mass spectrometry

Rapid quantification of tenofovir in umbilical cord plasma and amniotic fluid in hepatitis B mono-infected pregnant women during labor by ultra-performance liquid chromatography/tandem mass spectrometry
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超高效液相色谱/串联质谱法快速定量乙型肝炎单一感染孕妇分娩时脐带血浆和羊水中的替诺福韦

DOI:
10.1002/rcm.8728
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发表时间:
2020-05-15
影响因子:
2
通讯作者:
Lin, Nengming
Lin, Nengming
中科院分区:
化学3区
文献类型:
--
作者:
Ma, Zhiyuan;Li, Siying;Lin, Nengming

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替诺福韦(TFV)是一种抗乙肝病毒的一线药物,被推荐用于预防乙肝病毒的母婴传播。为了解乙肝病毒感染孕妇脐带血和羊水中TFV的分布情况,建立了一种快速、灵敏的检测TFV的方法,并进行了验证。在Acquity UPLC HSS T3色谱柱上,甲醇和0.01%氨水溶液在10 mM醋酸铵/水中进行梯度洗脱。这是首次报道的使用碱性流动相而不是酸性流动相测定TFV的方法。结果TFV的检测在4min内即可完成。TFV定量标准曲线在1~500 ng/m L范围内线性关系良好。批内、批间精密度和准确度为-4.35%~6.92%。该方法已成功地用于50例接受富马酸替诺福韦治疗的单一乙肝病毒感染者的测定。脐带血和羊水中TFV的平均浓度分别为29.2(4.6~86)ng/m L和470.9(15 6~90 2)ng/m L,两者呈中度正相关(r=0.5299,P
Rationale Tenofovir (TFV) is a first-line antiviral agent against hepatitis B virus (HBV) and is recommended for the prevention of mother-to-infant transmission of HBV. To study the distribution of TFV in umbilical cord plasma and amniotic fluid of HBV-infected pregnant women, a rapid and sensitive method for TFV determination was developed and validated.Methods The quantification method was developed using liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS). The analytes were separated on an Acquity UPLC HSS T3 column under gradient elution with methanol and 0.01% ammonia solution in 10 mM ammonium acetate/water. This is the first reported method for the determination of TFV using alkaline rather than acidic mobile phases. Linearity, accuracy, precision, limit of quantification, specificity and stability were assessed.Results Detection of TFV was achieved within 4 min. The calibration curves for TFV quantification showed excellent linearity in the range of 1-500 ng/mL. The intra- and interbatch precision and accuracy ranged from -4.35% to 6.92%. This method was successfully applied to determination of samples from 50 HBV mono-infected women undergoing tenofovir disoproxil fumarate therapy. The mean concentrations of TFV in the umbilical cord and amniotic fluid samples were 29.2 (4.6-86) and 470.9 (156-902) ng/mL, respectively, which showed a moderate positive correlation (r = 0.5299, P