TOF-MS method development

[pstaunton]

I was just wondering if somebody could give me details of websites and/or books that deal with Mass spectrometry method development (for the pharmaceutical industry)in a stepwise fashion.

I understand that details change from method to method but just something like a template would be helpful to give me the big picture. If it could relate to time of flight MS that would be great. Thanks

[Don_Hilton]

If this is for setting up instrument methods for LC (or GC) and Mass Spec, I would suggest that you check to see what the vendor has available. This may be the training class workbook. This would give you an organized way to go about setting up instrumental parameter with the exception of the details on how to establish the optimum analytical separation.

Development of a separation is a bit more detailed and this leads you off to books on the chromatographic techniques.

Your question could cover anywhere from instrument setup to development of a whole method from extraction to data processing – which is a bit much for a template. If you will provide a bit of clarification of the scope of the information you need, that may help.

[pstaunton]

Thank you mr. Hilton for your reply.

I understand that my question was lacking in detail.

The pharmaceutical company that I work for recently purchased a new TOF-MS(there very first MS)and I think they will be using it for impurities analysis.

I was just curious to know how much of a challenge the MS system would require to develop compared to the Actual chromatography of the sample.

Would the MS system be developed after the liquid chromatography?

[Don_Hilton]

This depends on the question you are trying to answer -- and what you already know.

If you have a list of degredation products, you may want to optimize source conditions (infusion of the analytes) before workign out the separation. Be sure you can detect it - then detect it after you separate it. (I'm not an LC guy - but from what I've watched, this seems to be what I see going on.)

If you do not have a list of degredation products, you don't have many options other than to try a sepration and turn on the mass spec and see what you can see.

If you have located degredation products by another technique, such as LC with UV detection, you have the separation already worked out -- as long as it is a moble phase that you can run into MS.

For steps in setting up the methods - take the training the instrument manufacturer offers for new users. This topic covered - at least by the manufacturers I am familiar with.

You have some restriction on what you can use in the moble phase - non-volatile salts tend to collect at the front end of the MS (not good) so you avoid them. But you have restrictions with other detectors. So in a way, a separation is a separation - and it feeds a detector. And, a TOF is a nice detector. I have a couple of GC-TOF systems in the lab - and I like them.

[pstaunton]

So first inject pure standards of impurities (if available) by direct infusion into the mass spectrometer to ensure detection and then start on working on the chromatography to ensure separation of all impurities.

Thanks again Mr. hilton.