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高效液相色谱法测定脑组织和血浆中的莫西沙星:在李斯特菌脑部感染的小鼠模型中的药代动力学研究中的验证。

High-performance liquid chromatography assay for moxifloxacin in brain tissue and plasma: validation in a pharmacokinetic study in a murine model of cerebral listeriosis.

机构信息

Laboratoire de Suivi Thérapeutique et de Contrôle des Médicaments, Service de Pharmacie, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Necker-Enfants Malades, 75015 Paris, France.

出版信息

J Anal Methods Chem. 2012;2012:436349. doi: 10.1155/2012/436349. Epub 2012 Mar 14.

Abstract

Moxifloxacin is a broad-spectrum antibacterial 8-methoxy-fluoroquinolone. In order to evaluate the pharmacokinetic properties of moxifloxacin in mouse plasma and brain tissue, we developed a high-performance liquid chromatography (HPLC) method. This study was based on single-drug delivery, intravenously dosed in a central listeriosis murine model. The method employed a reversed-phase Lichrospher RP-18 with a precolumn (250 × 4.6 mm) and a mobile phase composed of a mixture of acetonitrile, methanol, and citric buffer (pH = 3.5) with sodium dodecyl sulfate and tetrabutylammonium bromide. Fluorescence detection was performed at an excitation wavelength of 290 nm and an emission wavelength of 550 nm. The relative standard deviation of intra- and inter-day assays was <10%. This validated method led to a short retention time (8.0 min) for moxifloxacin. The standard curves were linear from 5-250 μg/L in plasma and from 0.1-2.5 μg/g of brain tissue. The limits of quantification were 5 μg/L in plasma and 0.1 μg/g in brain tissue. The method enabled the detection of systemic antimicrobial in plasma and in CNS in Listeria-infected mice. Injected moxifloxacin passed through the encephalic barrier within a 30 to 60 min after injection time frame. Moxifloxacin pharmacokinetics are modeled in an infected model compared to control mice.

摘要

莫西沙星是一种广谱抗菌 8-甲氧基-氟喹诺酮。为了评估莫西沙星在小鼠血浆和脑组织中的药代动力学特性,我们开发了一种高效液相色谱(HPLC)方法。这项研究基于单药给药,在中枢李斯特菌感染的小鼠模型中静脉注射。该方法采用反相 Lichrospher RP-18 预柱(250×4.6mm)和由乙腈、甲醇和柠檬酸缓冲液(pH=3.5)与十二烷基硫酸钠和四丁基溴化铵组成的流动相。荧光检测采用激发波长 290nm 和发射波长 550nm。日内和日间测定的相对标准偏差<10%。该验证方法导致莫西沙星的保留时间较短(8.0min)。血浆中的标准曲线在 5-250μg/L 范围内,脑组织中的标准曲线在 0.1-2.5μg/g 范围内呈线性。血浆中的定量限为 5μg/L,脑组织中的定量限为 0.1μg/g。该方法能够检测李斯特菌感染小鼠血浆中的全身性抗菌药物和中枢神经系统(CNS)中的药物。注射的莫西沙星在注射后 30 至 60 分钟内穿过血脑屏障。与对照小鼠相比,在感染模型中对莫西沙星的药代动力学进行了建模。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5f9/3335337/59d85d21b6ff/JAMC2012-436349.001.jpg

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