How to overcome blank interference at NDBA

Confirmatory Testing & Analytical Challenges
1

I am consistently observing blank interference at the NDBA retention time while analyzing small nitrosamines using LC-MS/MS. Currently, I am applying blank correction as a temporary measure.

How can I systematically troubleshoot and eliminate this blank interference? What could be the possible sources ?

2

Check contamination from filters, syringe, etc

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3

Check you method step by step in reverse order: 1) LCMS instrument blank"; 2) final solvent blank in vial; 3) filtered final solvent blank in vial… and so on

Just curious, did you figure out, what is the structure or exact mass of the interfering compound?

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The most common sources of contamination may come from solvents in the lab, instrument systems, consumables, etc. As RenatS mentioned, you can systematically check different blanks to identify the source of contamination. We have performed NDBA method development and detection many times, and NDBA contamination is very uncommon. We recommend thoroughly checking the brands of consumables and reagents you are using, as well as cleaning the injection needle and selecting an appropriate needle rinse solvent.

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Just searching this site, you can see that NDBA contamination from plastic is quite common:

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You can eliminate blank interference using a ghost-buster column. You will get a clean baseline. Please try this if your problem isn’t solved yet. If it is already solved, please share your experience.

Regards

Sriram.

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7

Waters gave a presentation about something similar to this last week, not for NDBA specifically, but for another small molecule nitrosamine.

There are several potential fixes, suggested elsewhere in the responses to your question, including potentially looking at other suppliers of your solvents etc. and your water. The new part they were presenting was the use of a delay column to separate the interference from the peak of interest. They also have a paper available on minimizing the noise and interference, I don’t know if that includes the delay column information now or not.

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Yep. I was just going to say that. It’s available on demand now The Next Frontier in Nitrosamines Testing: Detection and Risk Assessment in Packaging and IV Infusion Bags

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Regarding delay column vs NDBA, an app note is available on Waters website

https://www.waters.com/nextgen/us/en/library/application-notes/2026/the-use-of-a-delay-column-to-mitigate-persistent-interference-peaks-in-the-trace-level-quantitation-of-ndba-in-normal-saline-intravenous-infusion-bags-using-uhplc-ms-ms.html

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