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一种经过验证的用于定量HIV阳性人类血浆中CCR5抑制剂马拉维若的高效液相色谱-质谱法。

A validated HPLC-MS method for quantification of the CCR5 inhibitor maraviroc in HIV+ human plasma.

作者信息

Simiele Marco, Baietto Lorena, Audino Alessio, Sciandra Mauro, Bonora Stefano, Di Perri Giovanni, D'Avolio Antonio

机构信息

Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy.

Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy.

出版信息

J Pharm Biomed Anal. 2014 Jun;94:65-70. doi: 10.1016/j.jpba.2014.01.031. Epub 2014 Jan 31.

Abstract

Maraviroc is a CCR5 inhibitor approved in 2007 for treatment of therapy experienced adult patients infected with CCR5-tropic HIV-1 virus. International guidelines for HIV therapy indicate a plasma concentration cutoff of maraviroc for response. We developed and validated a new HPLC-MS method to quantify maraviroc concentrations in human plasma. 6,7-Dimethyl-2,3-di(2-pyridyl)quinoxaline was used as internal standard and added to 100μL of plasma. Samples were then treated with 500μL of acetonitrile for the protein precipitation procedure. An analytical T3 Atlantis column (150mm×4.6mm i.d.) with a particle size of 5μm was used to separate the compounds and ions were detected at m/z 257.5 and 313.3 for maraviroc and quinoxaline respectively. The calibration curve was linear up to 2500ng/mL. The mean recovery of maraviroc was 89.1%. All validation data results were in accordance to Food and Drug Administration and European Medicines Agency requirements. The HPLC-MS method reported here could be used routinely to monitor plasma concentrations of maraviroc in HIV-infected patients.

摘要

马拉维若为一种CCR5抑制剂,于2007年获批用于治疗感染CCR5嗜性HIV-1病毒的成年患者。国际HIV治疗指南指出了马拉维若产生疗效的血浆浓度临界值。我们开发并验证了一种新的HPLC-MS方法,用于定量测定人血浆中马拉维若的浓度。使用6,7-二甲基-2,3-二(2-吡啶基)喹喔啉作为内标,并将其加入100μL血浆中。然后用500μL乙腈对样品进行蛋白沉淀处理。使用粒径为5μm的分析型T3 Atlantis柱(150mm×4.6mm内径)分离化合物,分别在m/z 257.5和313.3处检测到马拉维若和喹喔啉的离子。校准曲线在高达2500ng/mL时呈线性。马拉维若的平均回收率为89.1%。所有验证数据结果均符合美国食品药品监督管理局和欧洲药品管理局的要求。本文报道的HPLC-MS方法可常规用于监测HIV感染患者血浆中马拉维若的浓度。

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