Placebo, Impurity at same RT

[Sunjay]

Dear All

If a placebo peak and impurity peak is coming at same RT and we are not able to seprate them, then can use the substaration i.e. substrating the area of placebo form area of impurity peak?

Regards

[Rob Burgess]

Its probably not ideal, your method development phase is meant to circumvent such situations. If it is the result of new excipients in the formulation then your method should evolve as the product evolves.

PS. We've recently had a case where we have had a quite similar situation, although we have pin-pointed that some erroneous peaks appear to be coming from certain scintillation vials we are using for our impurity analyses!

[adam]

I agree, and would add the following.

If your excipient peak is significantly larger than your impurity peak, then you would essentially be obtaining a small number by the difference of two large numbers. This is not good from a statistical standpoint. Because of the way the error propogates - from the big numbers onto the small number - you would have a very high variability in the result.

[SIELC_Tech]

What is the nature of your impurity and excipinets? Have you tried to separate them? You are probably looking at very small amount (0.1%) and your measurements are not going to be accurate.
If you impurity has differnt nature you can play with pH and try to change ionization sate and thus change retention

[JM]

ideally one should try to separate impurity from placebo but if it is not possible, one should look at the nature of impurity and placebo peak. Is it degradation impurity ? does placebo peak increase on storage? etc . Be prepared to run placebo during every analysis including stability studies i.e you have to place placebo batch also on stability along with your product.

JM

[Sunjay]

Dear All

Thanks for your valueable comments.

The situation we have faced in one method for the trial formulation. We are working on method to separate the peaks.

Thanks/ Regards

[bookoon]

Have you checked the spectra of the impurity peak and the placebo peak using a PDA detector? If both the spectra matches there is a contamination problem and you have to look into the needle wash factor or sample preparation. Which make HPLC do you use?

Often due to very low response of imputy peaks, spectra obtained are not very clear. Inject larger volume if required.

[yogesh#14]

Hi,

I guess the subtraction method is not that advisable. It is better (or rather best) to seperate the placebo impurity from the main peak. Try to change the chromatographic method to achieve the (required) seperation . Try playing around with the pH of mobile phase, column temaprature ....

Regards,

Yogesh

[Albany-12303]

Can you change your sample prep in order to not extract the placebo peak?

Sometimes this works