title: Rapid structure elucidation of drug degradation products using mechanism-based stress studies in conjunction with LC-MS(n) and NMR spectroscopy: identification of a photodegradation product of betamethasone dipropionate.
abstract: Betamethasone dipropionate is an active pharmaceutical ingredient (API) that is used in various dosage forms of finished products for the treatment of inflammatory disorders. An unknown degradant was observed during a solution stability study of betamethasone dipropionate. An approach that combines LC-MS(n), mechanism-based stress studies, semi-preparative HPLC purification and structure elucidation by NMR spectroscopy was used to identify the unknown species. The key step of this approach is the design of relevant stress studies based on the plausible degradation mechanism that is revealed by the informative LC-MS(n) analysis. The appropriately designed mechanism-based stress studies not only verify the degradation mechanism but also produce enough quantities of the unknown species for further structure elucidation/confirmation by NMR spectroscopy. With this strategy, the unknown degradant was rapidly identified as lumibetametasone dipropionate, a photodegradation product of betamethasone dipropionate.
authors.affiliation: Global Quality Services-Analytical Sciences, Schering-Plough Corporation, 1011 Morris Avenue, Union, NJ 07083, United States.
authors.forename: Mingxiang
authors.initials: M
authors.lastname: Lin
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Alexei V
authors.initials: AV
authors.lastname: Buevich
authors.forename: Rebecca
authors.initials: R
authors.lastname: Osterman
authors.forename: Abu M
authors.initials: AM
authors.lastname: Rustum
mesh_terms: D000893:Anti-Inflammatory Agents / Q000032:analysis* / Q000737:chemistry; D001623:Betamethasone / Q000031:analogs & derivatives* / Q000032:analysis / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002853:Chromatography, Liquid / Q000379:methods; D004355:Drug Stability; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D013058:Mass Spectrometry / Q000379:methods
chemical_list: D000893:Anti-Inflammatory Agents; C544695:lumibetamethasone dipropionate; C011175:betamethasone-17,21-dipropionate; D001623:Betamethasone