Chromatography Forum

We recently ran an Assay method by HPLC for Codeine, using a USP reference standard for Codeine Phosphate. The purity of the standard is indicated as 99.8%, but the standard method of analysis is by titration. If an the peak purity was determined just by the areas on the chromatogram (there are a number of small peaks in addition to the big drug substance peak), the purity might be more like 98.6%. There is an obvious flaw in trying to use a purity value obtained by one method (titration) for another method (HPLC).

Does anyone know a reputable reference standard supplier that sells Codeine Phosphate with the C of A determined by chromatography?

For Clarification, I should add that this is for an Assay analysis, with the specifications of 98.5% to 101.5%. Therefore, a change in the purity factor of the standard of < 1% can easily mean the difference between passing and failing.

This is not a direct answer to your question, but be very, very afraid of purity measurements based on area% on a chromatogram. The area% will only equal the mole% if all compounds have exactly the same absorbance at the detection wavelength (I'm assuming UV detection here). For area% to equal mass% further requires that all compounds have exactly the same molecular weight.

plus that you've seen all the impurity peaks, they aren't coeluting with the analyte, or off the end of the run time. Area% isn't good for absolute purity assignment, you want to be doing an external standard assay really. If the C of A states the actual purity then you're fine, if it just says ">99.8%" or whatever then it doesn't tell you so much.

you are trying to second check the purity of the USP standard or to get the purity of your own material using a USP standard?

if you are trying to re-check the USP standard purity, why are you trying to do so?
a USP standard is by design something you pay a lot of money for so that you can safely trust it and not need to second guess it.
this is what allows you to use your own working and very much less expensive in-house standard