Use of liquid chromatography/tandem mass spectrometric molecular fingerprinting for the rapid structural identification of pharmaceutical impurities.
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.
Global Quality Services-Analytical Sciences, Schering-Plough Corporation, 1011 Morris Avenue, Union, NJ 07083, USA. min.li@spcorp.com
Min
M
Li
Xin
X
Wang
Bin
B
Chen
Mingxiang
M
Lin
Alexei V
AV
Buevich
Tze-Ming
TM
Chan
Abu M
AM
Rustum
D001623:Betamethasone / Q000031:analogs & derivatives* / Q000737:chemistry; D002853:Chromatography, Liquid / Q000379:methods*; D004340:Drug Contamination; D007536:Isomerism; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D053719:Tandem Mass Spectrometry / Q000379:methods*
D004364:Pharmaceutical Preparations; C028994:betamethasone sodium phosphate; D001623:Betamethasone