Simiele Marco, Ariaudo Alessandra, De Nicolò Amedeo, Favata Fabio, Ferrante Martina, Carcieri Chiara, Bonora Stefano, Di Perri Giovanni, De Avolio Antonio
University of Turin, Department of Medical Sciences,(2) Laboratory of Clinical Pharmacology and Pharmacogenetics,(3) Amedeo di Savoia Hospital, CorsoSvizzera 164, 10149, Turin, Italy; "CoQuaLab", Academic Apin-off of University of Turin, Italy.
University of Turin, Department of Medical Sciences,(2) Laboratory of Clinical Pharmacology and Pharmacogenetics,(3) Amedeo di Savoia Hospital, CorsoSvizzera 164, 10149, Turin, Italy.
J Pharm Biomed Anal. 2017 May 10;138:223-230. doi: 10.1016/j.jpba.2017.02.002. Epub 2017 Feb 3.
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 (50:50v/v) followed by sample dilution with water. Chromatographic separation was performed on a Acquity UPLC HSS T3 column (150mm x 2.1mm I.D) with a particle size of 1.8μm 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.
利匹韦林（RPV）、多替拉韦（DTG）和埃替拉韦（EVG）是最新批准用于治疗HIV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并无用处。这种信息缺乏部分是由于缺乏一种高通量方法来同时定量这些药物和其他抗逆转录病毒药物。在这项工作中，我们描述了一种新的超高效液相色谱-串联质谱（UPLC-MS/MS）方法的开发和验证，该方法用于定量人血浆中的这些药物以及其他十四种抗逆转录病毒药物。向100微升血浆样品中加入内标（6,7-二甲基-2,3-二（2-吡啶基）喹喔啉），用甲醇：乙腈（50:50 v/v）进行简单的蛋白沉淀，然后用水稀释样品。在粒径为1.8μm的Acquity UPLC HSS T3柱（150mm×2.1mm内径）上进行色谱分离，并用串联质谱检测器检测化合物，监测每种药物的两个离子跃迁。RPV、DTG和EVG的平均回收率分别为101%、87%和112.3%。根据美国食品药品监督管理局指南要求，所有药物的日间/日内准确度和精密度均低于15%。本文报道的UPLC-MS/MS方法可常规用于监测包括RPV、DTG和EVG在内的抗病毒药物的血浆浓度。
