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ENANTIOSELECTMTY OF MASS SPECTROMETRY: CHALLENGES AND PROMISES

机译:质谱的对映选择性:挑战和承诺

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With the fast growing market of pure enantiomer drugs and bioactive molecules, new chiral-selective analytical tools have been instigated including the use of mass spectrometry (MS). Even though MS is one of the best analytical tools that has efficiently been used in several pharmaceutical and biological applications, traditionally MS is considered as a "chiral-blind" technique. This limitation is due to the MS inability to differentiate between two enantiomers of a chiral molecule based merely on their masses. Several approaches have been explored to assess the potential role of MS in chiral analysis. The first approach depends on the use of MS—hyphenated techniques utilizing fast and sensitive chiral separation tools such as liquid chromatography (LC), gas chromatography (GC), and capillary electrophoresis (CE) coupled to MS detector. More recently, several alternative separation techniques have been evaluated such as supercritical fluid chromatography (SFC) and capillary electrochromatography (CEC); the latter being a hybrid technique that combines the efficiency ofCE with the selectivity ofLC. The second approach is based on using the MS instrument solely for the chiral recognition. This method depends on the behavioral differences between enantiomers towards a foreign molecule and the ability of MS to monitor such differences. These behavioral differences can be divided into three types: (i) differences in the enantiomeric affinity for association with the chiral selector, (ii) differences of the enantiomeric exchange rate with a foreign reagent, and (Hi) differences in the complex MS dissociation behaviors of the enantiomers. Most recently, ion mobility spectrometry was introduced to qualitatively and quantitatively evaluate chiral compounds. This article provides an overview of MS role in chiral analysis by discussing MS based methodologies and presenting the challenges and promises associated with each approach. ? 2013 Wiley Periodicals, Inc. Mass Spec Rev 32:466-483,2013
机译:随着纯对映异构体药物和生物活性分子市场的快速增长,已经催生了新的手性选择性分析工具,包括使用质谱(MS)。尽管质谱仪是已在多种药物和生物学应用中有效使用的最佳分析工具之一,但传统上质谱仪仍被视为“手性盲”技术。该限制是由于MS无法仅基于它们的质量来区分手性分子的两个对映异构体。已经探索了几种方法来评估MS在手性分析中的潜在作用。第一种方法取决于MS的联用技术,该技术利用快速灵敏的手性分离工具,例如液相色谱(LC),气相色谱(GC)和与MS检测器耦合的毛细管电泳(CE)。最近,已经评估了几种替代分离技术,例如超临界流体色谱(SFC)和毛细管电色谱(CEC);等等。后者是一种混合技术,将CE的效率与LC的选择性结合在一起。第二种方法基于仅将MS仪器用于手性识别。此方法取决于对映异构体之间针对外来分子的行为差异以及MS监测此类差异的能力。这些行为差异可分为三种类型:(i)与手性选择剂缔合的对映体亲和力差异;(ii)与外来试剂的对映体交换速率差异;以及(Hi)复杂MS解离行为差异对映体。最近,引入了离子迁移谱法以定性和定量地评价手性化合物。本文通过讨论基于质谱的方法论并提出与每种方法相关的挑战和希望,概述了质谱在手性分析中的作用。 ? 2013 Wiley Periodicals,Inc.质谱Rev 32:466-483,2013

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