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.