LC-MS and NMR determination of a dichloromethane artifact adduct, cyproheptadine chloromethochloride.
The British Pharmacopoeia (BP) monograph for cyproheptadine HCl tablets requires a 'Related substances' thin-layer chromatography (TLC) test. This test revealed an extraneous spot with an R(f) of 0.1 in certain cyproheptadine HCl tablets that were under ambient retention conditions as well as those on stability programs. An investigation utilizing LC-MS, direct infusion MS, NMR, and organic synthesis has identified that the spot results from the N-oxide of cyproheptadine (a genuine degradate) and a co-eluting cyproheptadine-dichloromethane adduct, an artifact formed during the sample extraction step in which dichloromethane is used in the extracting solvent.
Li
Min
M
Regulatory and Analytical Sciences-Analytical, Merck and Co., Inc., WP82-30, P.O. Box 4, West Point, PA 19486, USA. min_li@merck.com
Ahuja
Eric S
ES
Watkins
Diana M
DM
D016477:Artifacts; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D003533:Cyproheptadine / Q000032:analysis*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008752:Methylene Chloride / Q000032:analysis*; D012702:Serotonin Antagonists / Q000032:analysis*; D012997:Solvents; D013237:Stereoisomerism; D013607:Tablets
D012702:Serotonin Antagonists; D012997:Solvents; D013607:Tablets; D003533:Cyproheptadine; D008752:Methylene Chloride