UPLC-MS/MS method for the simultaneous quantification of three new antiretroviral drugs, dolutegravir, elvitegravir and rilpivirine, and other thirteen antiretroviral agents plus cobicistat and ritonavir boosters in human plasma
UPLC-MS/MS method for the simultaneous quantification of three new antiretroviral drugs, dolutegravir, elvitegravir and rilpivirine, and other thirteen antiretroviral agents plus cobicistat and ritonavir boosters in human plasma
复制标题
DOI：
10.1016/j.jpba.2017.02.002
复制
发表时间：
2017-05-10
影响因子：
3.4
通讯作者：
De Avolio, Antonio
中科院分区：
文献类型：
--
作者：
Simiele, Marco;Ariaudo, Alessandra;De Avolio, Antonio
阿匹韦林（RPV）、度鲁特韦（DTG）和埃替拉韦（EVG）是最新批准用于治疗艾滋病毒感染的抗逆转录病毒药物。目前，关于它们的药代动力学和药效学特性的信息很少，因此对这些药物进行治疗药物监测是无用的。本研究建立了一种新的高效液相色谱-串联质谱法（UPLC-MS/MS），用于定量测定人血浆中这些药物和其他14种抗逆转录病毒药物的浓度。（6，7-二甲基-2，3-二（2-吡啶基）喹喔啉）进行简单的蛋白质沉淀，用甲醇：乙腈（50：50 v/v），然后用水稀释样品。色谱分离在Acquity（R）UPLC HSS T3柱（150 mm x 2.1 mm I.D）上进行，粒径为1.8 μ m，化合物用串联质量检测器检测，监测每种药物的两个离子跃迁。根据美国食品药品监督管理局指南的要求，所有药物的日间/日内准确度和精密度均低于15%。本文建立的UPLC-MS/MS方法可用于RPV、DTG和EVG等抗病毒药物的血药浓度监测。(C)2017由Elsevier B. V.出版
Rilpivirine (RPV), dolutegravir (DTG) and elvitegravir (EVG) are the latest antiretroviral drugs approved for treatment of HIV infection. Currently, poor information is currently available concerning their pharmacokinetic and pharmacodynamic properties, thus making the use of therapeutic drug monitoring for these drugs not useful. This lack of information is partially due to the absence of an high-throughput method for their simultaneous quantification together with other antiretroviral drugs.In this work, we describe the development and validation of a new UPLC-MS/MS method to quantify these drugs, together with other fourteen antiretroviral agents, in human plasma.One hundred microliters of plasma samples were added with internal standard (6,7-Dimethyl- 2,3-di(2-pyridyl) quinoxaline), underwent a simple protein precipitation with methanol:acetonitrile (50:50 v/v) followed by sample dilution with water. Chromatographic separation was performed on a Acquity (R) UPLC HSS T3 column (150 mm x 2.1 mm I.D) with a particle size of 1.8 mu m and compounds were detected with a tandem mass detector, monitoring two ion transitions for each drugs.The mean recovery of RPV, DTG and EVG were 101%, 87% and 112.3% respectively. Accuracy and precision inter/intra-day were below 15% for all drugs, in accordance to Food and Drug Administration guidelines requirements. The UPLC-MS/MS method reported here could be used routinely to monitor plasma concentrations of antiviral drugs, including RPV, DTG and EVG. (C) 2017 Published by Elsevier B.V.