[Hocks88]

Hey everyone, hope all is good! 

I work in the pharmaceutical sector with cough/sore throat medicines and the such. I've been given a problem to answer for an upcoming interview but to be honest I'm a bit stumped. It goes a little something like this...

"You are asked to re-qualify a titrimetric method and discover that the endpoint is not clearly defined. Having made a number of amendments you find the sample titration works, but the standard does not. Suggest a reason for this and justify it."

If the problem was reversed and the standard titration worked okay but the sample titration did not, then i would instantly assume that there was interference caused by excipients in the sample. However, I can't for the life of me think why the sample titration would work whilst the standard does not?

Any input or suggestions would be greatly appreciated! Thanks in advance 

[Borek]

I suppose you have fine tuned your procedure for the sample?

[Hocks88]

I suppose you have fine tuned your procedure for the sample?

The reagents involved are not specified in the question, let alone performed the titration itself. Its more of a hypothetical question as to why such a problem would occur. As i say, if the standard worked but the sample didn't then the excipients are interfering with the reaction and the specificity is out, but I can't seem to work out why the problem would occur the other way around?

[Borek]

I understand the situation. That was intended to be a hint

[ironnica]

I can only imagine here based on the info given. How do you know that it is the sample titration that's giving an accurate result as opposed to the standard giving the accurate result?

You'd need to work the standard up to contain the binder etc that's going to be in the sample, to confirm that the other components/matrix of the tablet aren't messing with analysis

[curiouscat]

Interesting question. I can't see the answer with Borek's hint.

All I can think is what about the reverse of interference? Could the exepients contain something that actually aids the procedure?

[Borek]

What I was aiming at was that if the changes to the procedure were made in such a way it works nicely for the sample, they could have an exactly opposite effect on the standard titration.

Say, procedure calls for some agent to mask the impurities, and your sample contains a lot of impurities, so you find out using large amount of the masking agent makes your titration work. Then you repeat the same modified procedure when titrating the standard. But the standard doesn't contain the impurities, so you are adding too much masking agent and it can interfere with the titration itself.

[curiouscat]

What I was aiming at was that if the changes to the procedure were made in such a way it works nicely for the sample, they could have an exactly opposite effect on the standard titration.

Say, procedure calls for some agent to mask the impurities, and your sample contains a lot of impurities, so you find out using large amount of the masking agent makes your titration work. Then you repeat the same modified procedure when titrating the standard. But the standard doesn't contain the impurities, so you are adding too much masking agent and it can interfere with the titration itself.

Thanks. Makes sense.