If 20 microlit of a 5.0 mg/ml solution of the drug product is injected and the impurity is observed to be 0.2 %. What would this correspond to %w/w?

Industry problem or pharmacy school test question? :-)

i think %w/w means you have standard reference you can compare response factors, so if that all for your question then the answer is insuffcient info.

I assume when you measure 0.2% it is based on area percent of the detection method.
But what detection method is it?
UV ? Fluorescence? RI?

One has to know the wt/detector response of any and of EVERY component in a mixture to determine wt% of any single component of a known wt/vol solution, AND we have to separate every single component, NO overlapping peaks.

For example, if the major peak had half the response by weight compared to the impurity, then the 0.2% impurity was actually about 0.4% by weight, if there was nothing else in solution. But what if your 5mg/mL solution actually contained 10% water in the undissolved sample, then your area percent determination might not see that 0.5mg/mL water peak.

I hope I have been clear in my example.

Unless you are certain of these response factors (and usually we are not 100% certain we have no undetected components much less an accurate determination of the response factors of unknowns)

THERE IS NO CORRESPONDENCE of area percent to wt percent.

It may be approximated or guessed at, but never accurately determined unless you know all the above.

Rodney George
Supelco

Thanks for the detailed reply Rodney.

The measurement was conducted with a UV detector? and we are not able to see any other major impurity besides the once observed in the chromatogram even when gradients with higher organic content where used to check for less polar impurities.

You are suggesting that I determine the response factor of the impurity with respect to the main component. Should the response factor be 1.0 or between 0.9 and 1.1 then it can be taken as 1.0 as per BP and then it should be possible to estimate the amount of this impurity in %w/w (i.e. in Ug/mg of active).

The Moisture content for this substance is 0.38%.

In such cases would be better to develop a method for quantifying all the impurities by determing the response factors using the ratio of slopes from the linearity data and plugging in the area counts into the expression:

Individual related substances (%w/w)=
AT1/AS1*DS/DT*P/100*100*RF*W/C

where AT=Area counts for the impurity under consideration,
AS=area counts of the main active component in std solution
DS=dition factor of sample solution
P=Potency of the active's working std
W=average weight of tablet, in mg
C=label claim of the tablet.

Thanks once again Rodney.

In my past experience the sample (drug) was analyzed by sundry methods and a purity was assigned to this sample. Likewise any impurity was identified and synthesized in bulk, analyzed, and assigned a purity. Then given a known purity and making accurate wt/vol% solutions, response factors can be assigned to each impurity and to the sample peak. You are quite right, linearity data must also be determined for each detection method. It is a lot of work but that is why pharmaceuticals cost so much.

Rodney George

Anonymous, your formular is o.k. as long as you use 100% standard solutions. Then you have to show linearity from 0.1% to 120%, which might be tricky. In my opinion it is more convinient to use a 0.5% standard.
If you know the impurity and it has the _same_ chromophor the molar absorption should be same and the response factor should be 1 (assuming same molecular weight).

Alex