Global Quality Services-Analytical Sciences, Schering-Plough Corporation, 1011 Morris Avenue, Union, NJ 07083, USA.
Rapid Commun Mass Spectrom. 2009 Nov;23(22):3533-42. doi: 10.1002/rcm.4276.
Use of liquid chromatography/tandem mass spectrometric (LC/MS(n)) molecular fingerprinting is systematically demonstrated as a very effective tool for rapid structural elucidation of pharmaceutical impurities through a case study in which three isomers of betamethasone sodium phosphate (BSP) were rapidly identified as degradants formed due to the D-homoannular ring expansion of the steroid core structure of BSP in the solid state. The rapid structural elucidation of these degradants was achieved by matching or closely matching the UV profiles, molecular weights, and more importantly the fragmentation patterns obtained from the LC/MS(n) (n = 1 to 3) analysis of their enzyme-catalyzed hydrolytic products, respectively, with those of a D-homoannular isomer of betamethasone available in our LC/MS(n) molecular fingerprint database. This strategy of using LC/MS(n) molecular fingerprinting to obtain high-confidence structures of unknown species is then validated by structure verification through one- (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) experiments.
使用液相色谱/串联质谱（LC/MS(n)）分子指纹图谱被系统地证明是一种非常有效的工具，可通过案例研究快速阐明药物杂质的结构，其中三种倍他米松磷酸钠（BSP）的异构体被快速鉴定为由于 BSP 的甾体核心结构在固态下的 D-同环扩环而形成的降解产物。这些降解产物的快速结构阐明是通过分别匹配或非常接近匹配其酶促水解产物的 LC/MS(n)（n = 1 至 3）分析中获得的 UV 图谱、分子量，更重要的是碎片模式，与我们的 LC/MS(n) 分子指纹图谱数据库中可用的倍他米松 D-同环异构体的相应图谱进行匹配。然后，通过一维（1D）和二维（2D）核磁共振（NMR）实验的结构验证来验证使用 LC/MS(n) 分子指纹图谱获得未知物质高可信度结构的这种策略。
