Novel Liquid Chromatography-Tandem Mass Spectrometry Method for Simultaneous Detection of Anti-HIV Drugs Lopinavir, Ritonavir, and Tenofovir in Plasma
Novel Liquid Chromatography-Tandem Mass Spectrometry Method for Simultaneous Detection of Anti-HIV Drugs Lopinavir, Ritonavir, and Tenofovir in Plasma
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DOI：
10.1128/aac.02748-13
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发表时间：
2014-05-01
影响因子：
4.9
通讯作者：
Ho, Rodney J. Y.
中科院分区：
文献类型：
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作者：
Koehn, Josefin;Ho, Rodney J. Y.
对于HIV感染，抗HIV药物组合通常用作高效抗逆转录病毒疗法（HAART），旨在最大限度地抑制病毒。三种经常联合使用的药物是蛋白酶抑制剂洛匹那韦和利托那韦以及核苷酸逆转录酶抑制剂替诺福韦。我们已经成功地开发了一种简单，高效，灵敏的方法，同时提取和测定血浆样品中洛匹那韦，利托那韦，替诺福韦的浓度。使用液-液提取进行血浆提取，然后对剩余水层进行蛋白质沉淀。合并收集的级分，干燥，并在移动的相中复溶。使用液相色谱-串联质谱法对药物进行定量。该测定法应用于两种灵长类动物（Macaca nemestrina）的血浆药物水平研究。生物分析方法进行了优化和验证，表现出较高的提取效率和良好的灵敏度和重现性。当在灵长类动物研究中应用该测定法时，在皮下给药后几分钟内，可在血浆中检测到所有三种药物。这种经过验证的测定方法将有助于以有效、选择性和灵敏的方式评价药物浓度。
For HIV infection, anti-HIV drug combinations are typically used as highly active antiretroviral therapy ( HAART), intended to maximize viral suppression. Three drugs used frequently in combination are the protease inhibitors lopinavir and ritonavir and the nucleotide reverse transcriptase inhibitor tenofovir. We have successfully developed a simple, efficient, and sensitive method to simultaneously extract and determine the concentrations of lopinavir, ritonavir, and tenofovir in plasma samples. The plasma extractions were performed using a liquid-liquid extraction followed by protein precipitation of the remaining aqueous layer. The collected fractions were combined, dried, and reconstituted in the mobile phase. The drugs were quantified using liquid chromatography coupled with tandem mass spectrometry. The assay was applied to a study of plasma drug levels in two primates ( Macaca nemestrina). The bioanalytical assay was optimized and validated to exhibit a high extraction efficiency and good sensitivity and reproducibility. When the assay was applied in a primate study, all three drugs could be detected in plasma within minutes of subcutaneous dosing. This validated assay will be useful for evaluation of drug concentrations in an efficient, selective, and sensitive manner.