Dear All, I am looking for a opinion in regards n-Nitroso clozapine (NDSRI) in Clozapine. As per my work experience, impurity behavior is very inconsistence when spiked in samples during analytical method development by using LCMS. If anyone developed the method please provide some clue to move forward.
Dear DPandey,
Your observation of inconsistent impurity behavior when spiked suggests that N-nitroso clozapine (NDSRI) might be undergoing transformation or interaction within the sample matrix. Have you observed any trends in its response over time, specific to sample preparation steps? Some additional considerations:
- Matrix Effects:Have you tested different excipients or formulation components separately to isolate any impact? Some NDSRIs show unexpected interactions with specific matrices.
- Secondary Decomposition Pathways: Could there be an oxidative or reductive transformation occurring under your conditions? A control experiment with alternative redox conditions might be insightful.
- Adduct Formation or Ion Suppression: In LC-MS, certain nitrosamines can exhibit adducts or ion suppression effects that may lead to apparent inconsistencies. Have you checked for secondary peaks or unexpected mass shifts?
- pH Sensitivity in Sample Prep: If using acidic or basic conditions during extraction, have you checked the stability of NDSRI across different pH levels?
Would be great to know more details on your current method setup and whether the issue is specific to sample preparation, chromatographic conditions, or mass spectrometric response.
Best regards,
PT
Hi, In addition to what Patekas said, you can add small amount of ammonia to the sample solution to make pH higher and see if its helps. Try to avoid the sonication if you are doing it.