I had being develop a method of N-nitroso Metamizole Impurity C using LC-MS. And have some issue as below :
N-Nitroso Metamizole Impurity C peak is appears in diluent chromatogram (even tried to minimize contamination like using new glassware and vials, first and freah prepare of solvent (before taking reference standard), and using some of column (stationary phase))
N-nitroso Metamizole Impurity C peak is drifting (not come back baseline to baseline, so the peak is difficult to cut by integration automatic)
We using methanol as diluent, and mobile phase using mixture of formic acid and methanol, and then rinsing injector using 2%DMSO in methanol.
What Stationary Phase are you using ? We did not have an issues with drifting RTs.
However what we discovered is, that the Metamizole itself was undergoing on column formation of the nitrosamine, depending on the eluents used.
Acetonitrile was better and also we used an really small amount of formic acid. Not the typical 0.1%.. I would really try to avoid methanol for Metamizole as much as possible.
We using Biphenyl as stationary phase and using 0.05% formic acid as mobile phase A.
We tried Acetonitrile as diluent and mobile phase B, however the peak of N-Nitroso Metamizole is not far apart from Metamizole peak and make the peak form is not like a peak (wide peak tip).
Hello, based on your question, I have some preliminary thoughts and wonder if they could be helpful. First, you can try changing the needle wash solution; the source of blank contamination may be insufficient needle washing. You can also test with another instrument. Regarding baseline and chromatographic peak drift, appropriately extend the elution time of the method and ensure the pressure stabilizes before the next injection. In addition, as you mentioned, a biphenyl column and methanol were used as the elution reagent. I agree with Phil that acetonitrile may be a better choice under this system.