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提高药代动力学研究中 LC-MS 定量分析性能的策略。

Strategies for improving the quantitative bioanalytical performance of LC-MS in pharmacokinetic studies.

机构信息

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.

出版信息

Curr Drug Metab. 2012 Nov;13(9):1206-12. doi: 10.2174/138920012803341320.

DOI:10.2174/138920012803341320
PMID:22519367
Abstract

Quantitative bioanalysis is urgently required for the evaluation of pharmacokinetic properties of a drug and to demonstrate the body exposure to the parent drug and/or metabolite for interpretation of the efficacy and toxicity. New trends in drug discovery and development will be always posing challenges on LC-MS-based quantitative bioanalysis. The focus of this minireview is to highlight the commonly used strategies for improving the quantitative bioanalytical performance including overcoming matrix effects and improving MS detectability. "LC-electrolyte effects" and "pulse gradient chromatography" proposed by our group are new approaches that have also showed potential efficiencies on improving overall bioassay performance, including lowering lower limit of quantification (LLOQ), enlarging upper limit of quantification (ULOQ), decreasing matrix effects, and overcoming elutropic effects, etc.. They should also work well in metabolic profiling studies and other important analytical fields, such as food pesticide residue analysis, environmental analysis, clinical and forensic toxicology, doping control, and so on.

摘要

定量生物分析对于评估药物的药代动力学性质以及为了阐释药物的疗效和毒性来证明母体药物和/或代谢物在体内的暴露情况是非常必要的。药物研发的新趋势总是会对基于 LC-MS 的定量生物分析提出挑战。本篇综述的重点是强调改善定量生物分析性能的常用策略,包括克服基质效应和提高 MS 检测的灵敏度。我们小组提出的“LC-电解质效应”和“脉冲梯度色谱”是两种新方法,它们在提高整体生物测定性能方面也显示出了潜力,包括降低定量下限 (LLOQ)、扩大定量上限 (ULOQ)、降低基质效应和克服洗脱效应等。它们在代谢组学研究和其他重要分析领域也应该有很好的效果,如食品中农药残留分析、环境分析、临床和法医毒理学、兴奋剂检测等。

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