Chromatography Forum

Hi,
I am working on method validation for a LC -related substances method for Acetaminophen formulation & need to spike 4-aminophenol, an impurity of acetaminophen.However the USP impurity std or even the AR/GR grade chemical being too unstable in atmosphere has turned black. I tried to get pure crystals by means of sublimation but could not get.can anybody please let me know how this can be handled?
Also how this problem is handled in routine acetaminophen product analysis in QC where we need to determine 4-aminophenol using low load std of 4-aminophenol itself.Can we prepare a Working std of this by qualifying against USPRS. Is any Method of analysis for 4-aminophenol available?

Thanks.

Hi

Sorry have not handled the substance myself, but what you describe seems to fit literature, ie sensitive to light and air over time (turns purple/black). Beside the obvious to store the substance in an inert atmosphere (nitrogen?), there might be another possiblity unless someone with more experiance can help.

The substance seems to be availble as an HCl salt as well, many amine HCl salts are considerble more stable than in base form, so one possiblility unless a better suggestion is provided is to use a fresh USP RS (primary reference susbstance ) to qualify a secondary reference substance (SRS) based on a HCl salt. See ICH Q7a §11.17-19 for definitions.