Liu David Q, Sun Mingjiang, Wu Lianming
GlaxoSmithKline plc, Analytical Sciences, King of Prussia, PA 19406, USA.
Curr Opin Drug Discov Devel. 2010;13(6):748-57.
The elimination of organic impurities to produce highly pure drug substances is an important goal of process chemistry. For the detection of general impurities, hyphenated techniques (eg, liquid chromatography-mass spectrometry [LC-MS]) play a critical role in rapid structural identification (qualitative detection) and in understanding the mechanisms of formation of the impurities, enabling informed decisions to control and eliminate the impurities resulting from the chemical process where possible. Concern regarding genotoxic impurities (GTIs), which must typically be controlled at low parts-per-million limits, continues to increase, and significant advances have been achieved in recent years for the selective and sensitive quantitation (quantitative detection) of such impurities. Conventional detection techniques, such as ultraviolet (UV) detection, are often inadequate for the detection of potentially minute quantities of GTIs; therefore, various advanced MS-based detection strategies, either stand-alone or in conjunction with chemical approaches, are playing an increasing role in this field. The primary aim of this review is to highlight recent advances in qualitative and quantitative detection of impurities at trace levels, with a particular focus on GTIs.
去除有机杂质以生产高纯度原料药是工艺化学的一个重要目标。对于一般杂质的检测，联用技术（例如液相色谱 - 质谱联用[LC - MS]）在快速结构鉴定（定性检测）以及理解杂质的形成机制方面发挥着关键作用，从而能够在可能的情况下做出明智决策来控制和消除化学过程中产生的杂质。对于通常必须控制在百万分之几低限度的基因毒性杂质（GTIs）的关注持续增加，并且近年来在这类杂质的选择性和灵敏定量（定量检测）方面已经取得了显著进展。传统检测技术，如紫外（UV）检测，对于检测潜在痕量的基因毒性杂质往往不够充分；因此，各种先进的基于质谱的检测策略，无论是单独使用还是与化学方法结合使用，在该领域正发挥着越来越重要的作用。本综述的主要目的是突出痕量杂质定性和定量检测方面的最新进展，特别关注基因毒性杂质。
