N-Nitrosamines: One to Watch
Probable carcinogens – N-nitrosamines – continue to keep pharmaceutical companies in the crosshairs of health regulators. From the active drug substances to the final on-the-shelf products and (unless a robust scientific argument can be made soon) at every stage of the production process – regulators are demanding increased scrutiny on the presence of nitrosamines. Chemistry World have a great piece on the subject if you want some more background.
That would mean raw materials, intermediates and solvents would have to be tested as part of the release specification. Beyond the obvious increase in analysis, this could disrupt efforts to reduce their environmental impact through re-cycling solvents. Unfortunately, recycling solvents has been identified as a key risk for the accumulation of N-nitrosamines so it could be bit of a head scratcher for many within the chemical manufacturing process. This is one that we’ll certainly be keeping a close eye on.
Automated Method Development
In the meantime, we’ve been collaborating with Mark Harrison and Giorgio Blom at Astra Zeneca to develop and validate a reliable, robust automated method for nitrosamine determination in drug substance and drug product. We’re investigating both LC-MS/MS and GC-MS/MS methods, covering the full range of nitrosamines. It’s required us to dig deep into the experience of our team but it looks like this could be a very important project.
If you’re interested in nitrosamines, you should take a look at this application note we developed a few years ago. It details our fully automated system for preparing and analysing samples for NDMA in potable water using GC-MS.
Camilla Liscio and I (Dan Carrier) are looking forward to doing the work on this application. We’d love to to get your take on nitrosamines and the implications of regulators upping their scrutiny. Please send me an email with your thoughts.
CONTACT US for more information about our work with N-nitrosamines.