Challenges and advantages of using IC-MS in the pharmaceutical industry

Many troublesome toxic impurities are discovered too late in pharmaceutical products, resulting in pharmaceutical companies having to recall their therapies. Highly polar and ionic species can be particularly difficult to detect in pharmaceutical products.

In this SelectScience webinar, now available on demand, Bethany Jackson, senior scientist at AstraZeneca, will discuss how ion chromatography-mass spectrometry (IC-MS) can solve some of the challenges associated with detecting impurities in the pharmaceutical industry. Jackson will demonstrate how IC can be an alternative technique for polar ionic species — therefore making it a good tool for small polar impurities that might not have been possible to detect by other techniques.

Think you’d benefit, but missed the live event? Register now to watch the webinar at a time that suits you or read on for highlights from the Q&A session.

Why not use HPLC? And what were the benefits of going with IC instead when looking at pharmaceutical compounds?

BJ: The reason we didn't go with HPLC for the anion analysis is that we were interested in very small anions. If you're using a standard reverse phase column on an LC, it's difficult to get good retention of these compounds. And if you are getting that retention, it's normally because you've got a very high pH mobile phase, which then can cause problems with your column robustness, and the sensitivity would also not be great with the modifiers that you'll be putting into your LC chromatography and then going into your mass spec.

In addition, if you were to look at something like HILIC, although it has benefits over reverse phase, you've then got issues with the sample matrix. The re-calibration that's required for running HILIC columns make that analysis a lot more complicated. So, IC had benefits in terms of its compatibility with the compound of interest and not causing damage to any of the elements that we would need to provide the chromatography we wanted.

In your analysis, you used 20% acetonitrile. Why did you pick this solvent? And did you try other organic solvents?

BJ: We decided to use acetonitrile because we have quite a lot of solubility information on the compound of interest in acetonitrile, which helped us with the sample preparation elements of our research. Also, because we were doing cation exchange chromatography, we wanted to avoid any alcohol. We did think about the potentials of other solvents, but due to our understanding of how the sample interacts with the acetonitrile and the compatibility of the column and the suppressors, we thought that was a sensible place to start and it got us the results we needed.

The mass spectrometer used was a single quad, would it be better to use a higher-res mass spectrometer for more sensitivity?

BJ: In theory, a higher-res mass spectrometer could have improved the sensitivity, if you can remove some of the additional background noise. However, due to the types of ions that we are using, an interest in that mass range isn't always as applicable. The instrument that we're using has a very low cutoff, which means that you can get sensitivity down at the lower mass range. The bigger molecules that we might be interested in getting more elucidation information out of, we could probably look at finding alternative methods on an LC to study. For what we were doing, the single quad gave us the information we needed, and there was no point trying to use a more complex system set up when we didn't need that capability.

How can you reduce system contamination?

BJ: One of the main problems we've been having is contamination, particularly with the types of compounds that we're looking at as a lot of pharmaceutical compounds tend to be cations once they're in solution. Trying to reduce that contamination can be challenging. There are a few things that we've tried such as extra column cleans, as well as looking at changing our solvents away from just the standard 100% aqueous and adding some organic. One of the options that we're looking into going forward is looking at the sample preparation element and seeing if there is a way that we can do eliminate the matrix from the solution using SPE. That way you've only got your analyte of interest going on to your column, which will mean much cleaner chromatography and much less interference with the mass spec and the signals that you're seeing.

To learn more about how IC-MS can help in pharmaceutical discovery and troubleshooting, watch the full webinar here>>

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