N-Nitroso Vonoprazan impurity peak area variation observed during drug product analysis by LCMS

Confirmatory Testing & Analytical Challenges
1

N-Nitroso Vonoprazan impurity peak area variation observed during drug product sample analysis by LCMS. Anyone facing same problem during the sample analysis? The initial standard solution gives stable response (%C.V. of 6 standards : below 2.0) After test sample run, the standard solution bracketing area was drastically decreased. The method was validated and sample analysis was already done in past with same validated method.

Need expert advice or suggestions.

Thanks in advance.

2

We have had similar issues with other compounds.

Have you tried injecting several standards after a sample?

Does the area return to normal after some time?

You could also add a simple cleaning gradient between samples and standards.
Also, don’t forget to include a high-water step if your initial conditions are not already high in water.