Liu David Q, Wu Lianming, Sun Mingjiang, MacGregor Paul A
Analytical Sciences, GlaxoSmithKline, UW2940, P.O.Box 1539, 709 Swedeland Road, King of Prussia, PA 19406, USA.
J Pharm Biomed Anal. 2007 Jun 28;44(2):320-9. doi: 10.1016/j.jpba.2007.01.019. Epub 2007 Jan 19.
Structural elucidation of pharmaceutical impurities in drug substances and drug products is an important task in pharmaceutical analysis in various phases of drug development. Liquid chromatography-mass spectrometry (LC-MS) technologies play a key role in this task owing to their general attributes of superior selectivity, sensitivity and speed. Full scan and product ion scan analysis, providing molecular weight information and fragmentation data, respectively, offer rich structural information and allow proposal of candidate structures rather quickly. However, these proposed structures often lack certainty especially when dealing with structural isomers. On-line hydrogen/deuterium (H/D) exchange by LC-MS using D2O as the mobile phase component is a powerful tool for identifying active hydrogen atoms, thus constituting a simple strategy for distinguishing between isomeric structures which are sometimes difficult by product ion spectral data or accurate mass data. This review describes the typical experimental setup we use routinely in the laboratories for performing H/D exchange LC-MS experiments in conjunction with representative applications of the strategy in structural elucidation of pharmaceutical impurities.
原料药和制剂中药物杂质的结构解析是药物研发各个阶段药物分析中的一项重要任务。液相色谱-质谱联用（LC-MS）技术因其具有卓越的选择性、灵敏度和速度等普遍特性，在这项任务中发挥着关键作用。全扫描和产物离子扫描分析分别提供分子量信息和碎片数据，能提供丰富的结构信息，并能较快地提出候选结构。然而，这些提出的结构往往缺乏确定性，尤其是在处理结构异构体时。以重水（D₂O）作为流动相组分，通过LC-MS进行在线氢/氘（H/D）交换是识别活性氢原子的有力工具，因此构成了一种简单的策略，用于区分有时难以通过产物离子光谱数据或精确质量数据区分的异构体结构。本综述描述了我们实验室常规使用的典型实验装置，用于进行H/D交换LC-MS实验，并结合该策略在药物杂质结构解析中的代表性应用。
