When analyzing biological extract samples—such as maleic and fumaric acids—using a Cogent Diamond Hydride™ TYPE‑C Silica™ column, users may occasionally observe a sudden and significant drop in peak height after a series of successful injections.
In the scenario described, analysts achieved approximately 10 consistent injections with excellent retention‑time reproducibility (RSD ≈ 0.5%), followed by an abrupt 10‑fold decrease in signal intensity, while retention times remained unchanged.
Contrary to initial concerns, the column is typically not the root cause of this issue. The stability of retention times strongly suggests that the stationary phase remains fully functional. Instead, the problem is most commonly linked to the mass spectrometer’s ion source or nebulizer performance.
Contamination, partial clogging, or reduced ionization efficiency can lead to dramatic signal loss without altering chromatographic retention.
Recommended Corrective Actions
1. Inspect and Clean the Ion Source
Signal suppression is frequently caused by residue buildup or contamination inside the ion source. Routine cleaning helps restore ionization efficiency and resolve diminished peak height.
2. Check the Nebulizer Assembly
A partially blocked or malfunctioning nebulizer can disrupt droplet formation, resulting in reduced detector response even when chromatography remains unaffected.
3. Verify Sample Matrix and Injection Volumes
Biological extracts can be matrix‑rich; if troubleshooting persists after instrument maintenance, re‑evaluate sample cleanup steps to reduce potential ion‑source fouling.
4. Confirm System Sensitivity with a Standard
Run a clean standard to confirm whether the issue is specific to the extract matrix or tied to overall MS performance.
Why the Column Is Usually Not at Fault
Cogent Diamond Hydride™ columns are designed for stability and reproducibility, especially in mixed‑mode and ANP applications. When a column actually degrades, retention times or peak shapes will typically shift. Because retention times remain consistent in this scenario, the column is performing as intended.
Conclusion
A rapid drop in peak height during LC‑MS analysis—while retention remains stable—is overwhelmingly indicative of ion‑source maintenance needs, not column failure. Cleaning the ion source and inspecting the nebulizer resolves this problem in the majority of cases and restores normal peak intensity.
If additional assistance is needed, analysts may contact MicroSolv Technical Support for troubleshooting or application guidance.
