impurity in the solvent front??

[salfar]

Dear all,

I have a question concerning a chromatogram that I got from an API. In the solvent front from my blank I have only a little peak; in the solvent front from my API I have a large peak. Sometimes it is difficult to integrate, but in my last run I was able to integrate it and verified that it correponds to a large amount of what I suspect to be an impurity. As it is a chromatogram from an API, shall I consider that peak to be an impurity? Another batch from another supplier of API did not give the same front peak. It was really small.

What is everyone opinion? Shall I integrate that as an impurity?

Thank you in advance

Salfar

[tom jupille]

You cannot quantitate on the basis of something at or near t0. There is good reason for the FDA's "suggestion" that k' values should be >2.

If you suspect an unretained impurity, you should try with successively weaker mobile phases until you get decent retention. Alternatively, run a gradient starting at low %B.

[amaryl]

Dear all,

I have a question concerning a chromatogram that I got from an API. In the solvent front from my blank I have only a little peak; in the solvent front from my API I have a large peak. Sometimes it is difficult to integrate, but in my last run I was able to integrate it and verified that it correponds to a large amount of what I suspect to be an impurity. As it is a chromatogram from an API, shall I consider that peak to be an impurity? Another batch from another supplier of API did not give the same front peak. It was really small.

What is everyone opinion? Shall I integrate that as an impurity?

Thank you in advance

Salfar

If your working solvent for API is different from mobile phase see to it, its solvent strength is less than your working mobile phase conditions.

Diluent should of of lesser solvent strength than mobile phase to avoid peak splitting.

Try changing the batch of solvent, if you suspect its an impurity in solvent.

Regards,

Amaryl.

[syx]

I agree that it should be an impurity or contaminant. It may be synthesis process impurity or degradate. If you want to ensure it you may check the synthesis pathway and locate the possible impurity that may be occurred in the API. Other way, you should perform stability indicating assay. As Mr. Jupille said, if you want to determine the purity of your API, you may use less strength of mobile phase to get sufficient retention (k’>2).

[salfar]

Thank you for all your help.

I suppose it may be due to the purification process and I will follow your suggestions plus using LC-MS, if possible.

Thank you very much.

Salfar

[Rob Burgess]

I presume you are talking about about drug substance rather than drug product when relating to your API analysis (API is too suggestive!)

If you are analysing drug product it may be that your impurity is just an excipient. This is often the case for drug product impurity runs, excipients often elute with the solvent front.

[JM]

I suggest to pls check the type and amount of Residual solvent present in the API and is there any difference between two APIs on account of this.

It has happned couple of times that the unretained peak in API is the strong UV absorbing residual solvent. confirm it by spiking.

JM