Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, USA.
J Am Soc Mass Spectrom. 2010 Apr;21(4):559-63. doi: 10.1016/j.jasms.2009.12.015. Epub 2010 Jan 7.
We report here an automated method for the identification of N-oxide functional groups in drug metabolites by using the combination of liquid chromatography/tandem mass spectrometry (LC/MS(n)) based on ion-molecule reactions and collision-activated dissociation (CAD). Data-dependent acquisition, which has been readily utilized for metabolite characterization using CAD-based methods, is adapted for use with ion-molecule reaction-based tandem mass spectrometry by careful choice of select experimental parameters. Two different experiments utilizing ion-molecule reactions are demonstrated, data-dependent neutral gain MS(3) and data-dependent neutral gain pseudo-MS(3), both of which generate functional group selective mass spectral data in a single experiment and facilitate increased throughput in structural elucidation of unknown mixture components. Initial results have been generated by using an LC/MS(n) method based on ion-molecule reactions developed earlier for the identification of the N-oxide functional group in pharmaceutical samples, a notoriously difficult functional group to identify via CAD alone. Since commercial software and straightforward, external instrument modification are used, these experiments are readily adaptable to the industrial pharmaceutical laboratory.
我们在这里报告了一种通过使用基于液相色谱/串联质谱（LC/MS(n)）的离子-分子反应和碰撞诱导解离（CAD）相结合的方法，自动识别药物代谢物中 N-氧化物官能团的方法。数据依赖型采集已被广泛用于基于 CAD 的代谢物特征描述方法，通过仔细选择选择实验参数，适应了基于离子-分子反应的串联质谱。本文展示了两种利用离子-分子反应的不同实验，即数据依赖型中性增益 MS(3)和数据依赖型中性增益伪 MS(3)，这两种方法都可以在单个实验中生成官能团选择性质谱数据，从而提高未知混合物成分结构鉴定的通量。这些实验采用了先前为鉴定药物样品中 N-氧化物官能团而开发的基于离子-分子反应的 LC/MS(n)方法，该方法可以有效地识别单独使用 CAD 难以鉴定的官能团。由于使用了商业软件和简单的外部仪器修改，这些实验很容易适应于工业制药实验室。
