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药物代谢与药代动力学中的湍流生物分析

Turbulent flow bioanalysis in drug metabolism and pharmacokinetics.

作者信息

Rudewicz Patrick J

机构信息

Elan Pharmaceuticals, South San Francisco, CA 94080, USA.

出版信息

Bioanalysis. 2011 Jul;3(14):1663-71. doi: 10.4155/bio.11.137.

DOI:10.4155/bio.11.137
PMID:21756098
Abstract

Turbulent flow chromatography (TFC) as an analytical technique was introduced in the mid-1990s for online sample processing in bioanalysis. Turbulent flow columns are packed with large particles permitting the use of high mobile phase linear velocities. Solute molecules travel in a uniform concentrated band in which large matrix biomolecules are effectively separated from lower molecular weight analytes by differential mass transfer effects. In addition, the use of various bonded stationary phases enhances selectivity in TFC separations. Originally, the turbulent flow column was used for both online sample processing and the analytical separation. This mode of operation has largely been replaced with a dual column arrangement, in which sample processing is done online with the turbulent flow column and a second analytical column is employed for separation. Within the pharmaceutical industry, certain laboratories now use TFC routinely for bioanalytical support of in vivo drug discovery pharmacokinetic studies. Validated TFC methods are also used to support GLP-compliant preclinical toxicokinetic studies and clinical trials. TFC has been shown to simplify bioanalytical sample preparation and reduce sample processing costs when compared with offline techniques such as SPE. TFC may be combined with multiplexing up to four HPLC systems to a single mass spectrometer to increase analytical throughput.

摘要

湍流色谱法(TFC)作为一种分析技术于20世纪90年代中期被引入,用于生物分析中的在线样品处理。湍流柱填充有大颗粒,允许使用较高的流动相线性速度。溶质分子在一个均匀的浓缩带中移动,其中大的基质生物分子通过差异传质效应与低分子量分析物有效分离。此外,使用各种键合固定相可提高TFC分离的选择性。最初,湍流柱用于在线样品处理和分析分离。这种操作模式在很大程度上已被双柱配置所取代,其中样品处理通过湍流柱在线进行,第二根分析柱用于分离。在制药行业,某些实验室现在常规使用TFC来支持体内药物发现药代动力学研究的生物分析。经过验证的TFC方法也用于支持符合GLP的临床前毒代动力学研究和临床试验。与离线技术(如固相萃取)相比,TFC已被证明可简化生物分析样品制备并降低样品处理成本。TFC可与多达四个HPLC系统多路复用至单个质谱仪,以提高分析通量。

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