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一种用于测定血浆中马拉维若浓度的简单液相色谱-质谱联用方法的开发与应用。

Development and application of a simple LC-MS method for the determination of plasma maraviroc concentrations.

作者信息

Takahashi Masaaki, Hirano Atsushi, Okubo Nami, Kinoshita Eri, Nomura Toshiharu, Kaneda Tsuguhiro

机构信息

Department of Pharmacy, National Hospital Organization Nagoya Medical Center, Aichi, Japan.

出版信息

J Med Invest. 2010 Aug;57(3-4):245-50. doi: 10.2152/jmi.57.245.

Abstract

Maraviroc is an orally available antagonist of the CCR5 chemokine receptor, which acts as a human immunodeficiency virus type 1 (HIV-1) coreceptor. Binding of maraviroc to this receptor blocks HIV-1 attachment to the coreceptor and prevents HIV-1 from entering host cells. Maraviroc does not require intracellular processing to exert this activity. Drug interaction studies have shown changes in maraviroc exposure when given with other anti-HIV medications, and thus quantification of maraviroc in human plasma is important to manage drug interactions and to evaluate the relationship between plasma concentrations and treatment response. We developed a conventional LC-MS method for determining plasma maraviroc concentrations, validated by estimating precision and accuracy for inter- and intraday analysis in the concentration range of 0.011-2.188 µg/ml. The calibration curve was linear within this range. The average accuracy ranged from 92.7% to 99.7%, while the relative standard deviations of both inter- and intraday assays were less than 7.1%. Recovery of maraviroc exceeded 86.7%. Our LC-MS method provides a conventional, accurate and precise way to determine the maraviroc concentration in human plasma. This method enables dose adjustment based on monitoring plasma maraviroc concentrations and permits management of drug interactions and toxicity.

摘要

马拉维若为一种口服有效的CCR5趋化因子受体拮抗剂,CCR5趋化因子受体作为1型人类免疫缺陷病毒(HIV-1)的共受体。马拉维若与该受体结合可阻断HIV-1与共受体的附着,并防止HIV-1进入宿主细胞。马拉维若发挥此活性无需细胞内加工。药物相互作用研究表明,与其他抗HIV药物联用时,马拉维若的暴露量会发生变化,因此测定人血浆中马拉维若的含量对于管理药物相互作用及评估血浆浓度与治疗反应之间的关系很重要。我们开发了一种用于测定血浆中马拉维若浓度的常规液相色谱-质谱(LC-MS)方法,通过估算浓度范围在0.011 - 2.188μg/ml之间的日间和日内分析的精密度和准确度进行验证。在此范围内校准曲线呈线性。平均准确度在92.7%至99.7%之间,而日间和日内测定的相对标准偏差均小于7.1%。马拉维若的回收率超过86.7%。我们的LC-MS方法提供了一种常规、准确且精密的方式来测定人血浆中马拉维若的浓度。该方法能够根据监测血浆中马拉维若的浓度进行剂量调整,并有助于管理药物相互作用和毒性。

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