title: Forced degradation of betamethasone sodium phosphate under solid state: Formation, characterization, and mechanistic study of all four 17,20-diastereomers of betamethasone 17-deoxy-20-hydroxy-21-oic acid.
abstract: Four diastereomers of betamethasone 17-deoxy-20-hydroxy-21-oic acid were found to be degradants of betamethasone sodium phosphate when the latter was stressed by heat under the solid state. The structure elucidation of these four diastereomers was achieved by a combination of LC-MS(n) (n = 1-3), various 1D and 2D NMR experiments, and mechanistic consideration of potential degradation pathways. A mechanism for the formation of the four degradants has been proposed, which involves hydration of a key intermediary degradant, betamethasone enol aldehyde, followed by intramolecular Cannizzaro reaction. The proposed mechanism is supported by a model reaction which converted betamethasone enol aldehyde into the four diastereomeric degradants in good yields, albeit in solution chemistry.
authors.affiliation: Global Quality Services - Analytical Sciences, Schering-Plough Corporation, 1011 Morris Avenue, Union, New Jersey 07083, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Bin
authors.initials: B
authors.lastname: Chen
authors.forename: Tze-Ming
authors.initials: TM
authors.lastname: Chan
authors.forename: Abu
authors.initials: A
authors.lastname: Rustum
mesh_terms: D001623:Betamethasone / Q000031:analogs & derivatives* / Q000737:chemistry; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D005938:Glucocorticoids / Q000737:chemistry*; D006358:Hot Temperature; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008956:Models, Chemical; D013056:Spectrophotometry, Ultraviolet
chemical_list: D005938:Glucocorticoids; C539653:betamethasone 17-deoxy-20-hydroxy-21-oic acid; C028994:betamethasone sodium phosphate; D001623:Betamethasone