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Troubleshooting High Backpressure in HPLC System

Discussions about HPLC, CE, TLC, SFC, and other "liquid phase" separation techniques.

4 posts Page 1 of 1
Hello everyone,

I’m encountering an issue with my HPLC system and could really use some advice. Recently, I’ve been experiencing unusually high backpressure during my runs, and I’m not sure what’s causing it. The system had been running fine with a C18 column (4.6 x 150 mm, 5 µm particle size) and an acetonitrile/water gradient (60:40), but now the backpressure is significantly higher than normal, even with the same mobile phase.

Here’s what I’ve tried so far:
  • Flushing the system with isopropanol and water to clean out any blockages.
    Replacing the guard column, thinking it might be clogged.
    Checking the fittings and connections for any leaks or signs of wear.
Despite these efforts, the pressure remains high. The column itself is relatively new (less than 300 injections), so I’m hesitant to think it’s a column issue. Has anyone experienced similar problems or have suggerailsstions on what else I can troubleshoot? Could this be a mobile phase issue or something with the pump?

Thanks in advance for any insights!
This exercise is called "logical troubleshooting", super useful whether dealing with a vehicle or a chromatography system.

In your instance, the first thing to do is remove the column and pump, and see if the pressure is higher than it should be. If that's OK, and re-installing the column causes the high pressure to still occur, I'd install the column backwards and flush that way. Most modern columns can be backflushed this way, and you would have nothing to lose by trying.
ConsumerProductsGuy wrote: "In your instance, the first thing to do is remove the column and pump, and see if the pressure is higher than it should be"
- For troubleshooting, we would recommend you leave the HPLC PUMP inline for testing! That would be the most logical way to start.

Next, install a restriction capillary in place of the column to obtain a reliable back-pressure for your system (maybe 50-75 bars?). Now you can test the system without a major variable in place, the column (which may be fouled).
Here is a link to a free article with more troubleshooting info: "Diagnosing & Troubleshooting HPLC Pressure Fluctuation Problems (Unstable Baseline)"; https://hplctips.blogspot.com/2014/01/d ... -hplc.html

Your post did not include many details so this is speculation, but it does sound like your column is probably fouled (first thing to replace) OR your pump's INLET FRIT (or solvent pickups) are clogged. Running IPA through a C18 does NOT clean or flush it (makes no sense). An appropriate flush solution must be developed based on the specific sample types and mobile phase use. Please contact an experienced, local chromatographer for more help.
4 posts Page 1 of 1

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