method development
Posted: Thu Jan 17, 2008 11:58 pm
Hi, say I was given a method to develop for the analysis of acetaminophen and its impurities (suppose we don't know what these are). Starting with the bulk drug, do I perform forced degradation studies on the acetaminophen. Acid/base/peroxide/temperature/light. I also prepare a fresh sample of acetaminophen prior to running the hplc.
Acetaminophen has an amide group which is very stable and not overly susceptible to interaction with acids or bases without heat. However, with heat amides can hydrolyse to the carboxylic acid via acid or base. Therefore, is para aminophenol a potential product or not?
I think the phenolic group can oxidise to a ketone, but I thought this to be more likely for diphenolic compounds.
Finally, from the web the pKa of acetaminophen is about 9.4. Therefore its probably best to run this analyte in low pH mobile phase. However, at this pH THE perhaps a phosphate buffer of pH3 using a C18 column based on modern silica, eg hypersil gold.
Wavelength of detection about 254nm.
Can someone please comment if my thinking is on the right track
Many thanks
Liv
Acetaminophen has an amide group which is very stable and not overly susceptible to interaction with acids or bases without heat. However, with heat amides can hydrolyse to the carboxylic acid via acid or base. Therefore, is para aminophenol a potential product or not?
I think the phenolic group can oxidise to a ketone, but I thought this to be more likely for diphenolic compounds.
Finally, from the web the pKa of acetaminophen is about 9.4. Therefore its probably best to run this analyte in low pH mobile phase. However, at this pH THE perhaps a phosphate buffer of pH3 using a C18 column based on modern silica, eg hypersil gold.
Wavelength of detection about 254nm.
Can someone please comment if my thinking is on the right track
Many thanks
Liv