You may have other oxidants (oxygen reactive species) in your drug other than molecular oxygen. For oxygen scavengers, you may try a different one. If this does not improve the outcome, you may have photooxidation. Perform all experiments protected from light, including sample preparation (fluorescent light in the hood can alter the samples during sample preparation). Include an unprotected sample for comparison.

Hi

Maybe you should try to make again some experiments with vials from another vendor (glass, impurities, metals), and if you are using try to explore different rubber vial stoppers compatibility. Maybe it's time to check how the drug product (solution) is prepared see below. Nitrogen is unreactive and inert because of high bond energy (N2) this is why probably the source of the problem is in solution inside, vial, or stoppers ....

"Usually during forced degradation studies in aqueous hydrolytic environment, dissolved oxygen and other gases are not removed with the help of nitrogen flushing. So, it may this dissolved oxygen that may generate some radicals from water and trigger these unconventional reactions."

https://www.ijper.org/sites/default/files/10.5530ijper.50.3.28.pdf

Hope it helps

Best regards

Tomasz

Hi Merel, Just for clarification, is this drug stable in the solvent? Paul.

Thank you all very much for your answers!! The drug is known to be sensitive for oxidation in the solid state. So indeed, the most likely explanation would be that there still is oxygen present to initiate something.. like the vial is not fully closed off but the samples were placed in a dark cabinet. The weird thing is that you would not expect it to happen more in a vial with a oxygen scavenger bag.

UPDATE: We found the solution..... the moisture scavenger bag contains moisture and is able to make a 75%RH.. so that explains the high degradation. So lesson learned: if you use oxygen scavenger bags, make sure they do not create moisture!