We recently received the standard for N-NITROSO-SERTRALINE, but we are not detecting the expected m/z 335 for the protonated ion of the molecule (C₁₇H₁₆Cl₂N₂O). Based on literature, the m/z 335 > 275 transition is commonly reported.
We are wondering if degradation of the standard might have occurred or if our source parameters are favoring the formation of other ions, such as m/z 275.
Has anyone worked on method development for this analysis? Any insights would be greatly appreciated!
Maybe this article helps. I have observed in-source fragmentation for some compounds, with losses of 30 Da and 48 Da. However, this does not match your results, correct?
Since your molecule has two chlorine atoms, you could check the isotopic distribution in an MS1 scan. It should look something like this:
We’ve seen in-source fragmentation to the M+ radical cation (losing the amine nitrogen and both the methyl and nitroso groups with it) presumably due to the benzylic carbon stabilizing such fragmentation. That’s the 275 ion. We were barely able to see the 335 ion and so went with 275 as the “parent ion”.
In our lab we found the same problem with Nitroso Orphenadrine. The m/z 181 was very intense, m/z 385 ([M+H]+ ), while present, had very very low intensity. So we concluded that in-source fragmentation was occurring.
As we didn´t want to use the MS2 as the “parent” ion, we optimized de source parameters as much as we could to enhance the intensity of m/z 385. It was not the most abundant ion, but we got an adequate signal to perform a MRM anlysis.
Hi, We had validated a Nitroso Sertraline method with the parent ion of 335. The best transitions that were find were 335 > 275, 335 > 159 and 335 > 123. Indeed the 335 it can be quite small, so we change sample preparation in order to have a higher LOQ solution in ng/mL.
One of the main parameters that usually affects this compounds is the source temperature. I was able to gain some sensibility/response with a lower source temperature (around 200 ºC).
We work with different suppliers (Agilent, Sciex, Waters) and for some compounds I observe significant changes in the abudance of parent ions and also fragments. This is related to the source and CID design, but strongly depend on NDSRI molecule stability.
Some N-nitroso derivatives are very easy to decompose in the source, especially compounds with a benzylmethylamine function.
Try to optimize the source parameters with a lower mobile phase flow (lower the temperature to reduce parent ion decomposition).
Try to optimize source and then MS/MS parameters on Your instrument. In some cases of N-nitroso compounds manual optimisation is necessary.
Hi Adriana,
We have already validate an analytical method for N-niroso-sertraline. At the begining, we had troubles using ESI source because we couldn´t see transition 335>275 but, have you tried APCI source?
The sensitivity will be lower but maybe it works for you.
You can solve this issue using lower ion source and transfer line temperatures (150ºC). Also adding ammonium formiate buffer to mobile phases might help to reduce sodium and potassium adducts and increase [M+H]+ signal
