Solution stability of NDSRI

hi, friend, I am working on a NDSRI, and I found that in some situation, the standard solution keeps stable within 1/2 days, while for some circumstance, the signal of standard solution decreases dramatically. the diluent I used is ACN/H2O (v/v = 6/4) + 1%formic acid. ACN from Merck or fisher, LC-MS grade; water from milli Q, formic acid from manufacture in China, analytic-grade.

I know adding the formic acid may lead in-situ formation, while for my study, I found this may decrease in both standard solution and sample solution. Pls help me and thanks all!

Hello, could you please let me know what NDSRI you are studying? The sensitivity to acids and bases varies for compounds with different structures.

hello,

did you use an LC-MS method? if yes, you could try to acquire a full scan, identify the possible possible degradation products and take some corrective action for preventing theis formation during standard preparation

Hello,

I found out that some NRSI can be quite sensitive to acids or bases or even water. I recommend to verify only in organic solvent if the same degradation occurs, without any other additives.

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the structure needs to be confidential. Do you have any insight that some specific functional group may be vulnerable under acidic condition? Big thanks!

I would try this. I also noticed that using ACN may be more stable than using MeOH as diluent.

Sure. Good idea! I can also use neutral loss scan of 30Da to identify the potential degradation products.

N-Nitrosamides, acetals/hemiacetals, or nitrosamines with an α-hydroxy group are unstable under acidic conditions. Additionally, as you mentioned, using acetonitrile as a diluent may provide greater stability compared to methanol. If your structure contains a nitrosamide moiety, hydrolysis and alcoholysis are possible. For unstable NDSRIs, in addition to optimizing the diluent, you can also try preparing the solution fresh just before use, and storing it at low temperature while protecting it from light.