I am in difficult situation on how to tackle this; how did this happen? I read the book, and the answer not really helping out. what the best solution to handle this situation. is it because my poor sample preparation or anything in regard of the instrumentation performance
In LC-MS/MS drug quantitation, "Ion Ratio Out" occurs when the qualifier-to-quantifier ion ratio deviates beyond acceptable limits, indicating matrix effects, poor sample preparation, or instrument issues. Causes include ion suppression, incomplete extraction, mass calibration drift, collision energy inconsistencies, and retention time shifts. Solutions involve optimizing sample cleanup (SPE over PPT), checking system suitability, tuning the MS, adjusting collision energy, and ensuring proper column performance. Regulatory guidelines require investigations for deviations. If QC samples pass but study samples fail, focus on matrix effects. If all fail, check instrument calibration. Reanalyzing standards can help pinpoint and resolve the issue.
"Ion Ratio Out" means the ion ratio in your LC-MS/MS analysis is off, usually due to sample prep issues or instrument problems. To fix it, improve sample prep (try SPE), check instrument calibration, and adjust settings like collision energy. If the issue only affects study samples, look for matrix effects. I agree with the earlier answer of Dr Balamurugan Krishnamoorthy
Noted Amit Kumar Tiwari . Thank you so much for your suggestion. I still don't get answer involving partial validation for adjusting instrument calibration and do I need to redo infusion of that particular standard drugs in LCMS/MS to get better CE?
Usually an ion ratio issue is showing that one of the ions / MRMs in the samples is in reality not generated from the analyte in question, but from something else.
a) invest into clean-ups is a good approach
b) check on whether other ions or transitions are available that could also be used is another one.
c) considering Your retention times (all around 1.5) investing into serious gradient chromatography will solve Your case most probably as well.
In my view the discussion on matrix effects ion suppresion etc would usually affect for ions/transitions.
good luck
Noel W Davies Already uploaded the correct one. Thank you for notifying me Thank you Kai Bester for the explanation.
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