Recently, we have had trouble with a dramatic decrease in general signal intensity by factor 10 of our MS (Triple Quad) also affecting intensity of mass calibrators (i.e. PPGs). While professional service including intensive cleaning of all parts and replacement of some parts (e.g. ion path before Q1 and detector) sufficiently solved the problem we are in search for the cause of this problem to avoid it in the future.
The signal decrease started around a time when an RP column was tried out for a new method development with a quite basic pH that obviously killed the column. While I have read about column bleeding being able to cause ion suppression and distinct interfering peaks within the run, does anyone have experience of HPLC-column bleeding having a long-lasting effect on MS performance even after the column was removed and the system has been cleaned, i.e. causing a true damage to the MS? Any sort of irremovable contamination that interferes with ionization or detection?
You may have contaminated the entire flow path of the instrument and/or damaged your vacuum degasser.
So called "column bleed" using modern HPLC columns with appropriate mobile phases is very, very rare. Far more common to abuse or damage the system (flow path) with chemically incompatible solvents or additives (these include ion-pairing agents, strong acids/bases too).
- "An Often Ignored HPLC & LC/MS Contamination Source. Did you check your Vacuum Degasser?"; https://hplctips.blogspot.com/2015/08/an-often-ignored-hplc-lcms.html
The MS was a Shimadzu 8060 triple quad instrument. And I just figured, it was a HILIC column that was accidentally used with an inappropriate mobile phase (too basic).
The problem was solved by professional service as mentioned in the starting post. The question is more about the root cause. Can the column bleed actually have caused the trouble with the MS or do we have to rule out other possible causes? I know about sample matrix components (e.g. phospholipids) being able to cause ionsuppression but rather temporarily at the start of the respective chromatogram an not affecting general signal intensity.
please check,
https://pharmaguides.in/internal-parts-of-distillation-column/
As already stated, "can column bleed cause such a problem?" Possible, but highly unlikely (modern commercial HPLC columns are not the issue, users are). Keep in mind that the LC-MS system is just a "dumb" tool. If not set up and used properly, with a proper method that follows good chromatography fundamentals, then frustration and poor quality results will result. So many systems I am called in to troubleshoot are used with chemically incompatible solvents or additives (these include ion-pairing agents, strong acids/bases too) and/or inappropriate settings. I see so many clients contaminate the flow path of their instruments by overloading columns with sample(s), running samples that are not 100% dissolved in the mobile phase, injecting samples that precipitate out into the mobile phase or are not compatible with the LC-MS/MS method(s) used (leading to source contamination).
The issue which should be addressed is training, or lack of and can be best addressed by insuring that all methods used are followed up with appropriate WASH methods (using solvents that are stronger than the mobile phase) to fully remove any left-over, retained material (reducing column fouling, carryover and flow path contamination).
- Optimizing all MS settings, Insuring samples are "appropriate" for analysis, fully dissolved in the mobile phase and use a high quality wash method, for each analysis, can go a long way to reducing contamination.
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