Leakage in your HPLC system: causes, detection and prevention
A practical guide to identifying and fixing leaks in analytical systems
Leakage in an HPLC system is one of the most common faults in the analytical laboratory. A leak introduces air into the system, changes the volume ratio and can create dangerous situations when volatile solvents are used. This article explains where leaks come from, how to track them down quickly and how to prevent them structurally.
⏱ approx. 5 minutes reading time
Where are leaks located in an HPLC system?
Virtually all leaks in analytical systems are found in the same locations. Systematically checking these points saves a lot of search time:
| Location | Cause | Signal |
| Pump (plungers) | Worn plunger seals or a damaged plunger | Drops or moisture visible around the pump head |
| Injector / autosampler | Worn rotor seal or stator | Leak around the injection block, peak variation between injections |
| Column connections (column inlet) | Incorrectly tightened fitting or wrong ferrule position | Leak precisely at the front, where the pressure is highest |
| Fittings throughout the system | Not properly tightened, damaged ferrule or cold-flowed seal | Drops or salt crystals around the fitting |
| Detector | Leakage from the flow cell or connecting capillaries | Moisture around the detector connection |
| Check valves | Blocked or worn (leads to an internal leak, not always visible) | Pressure instability, irregular flow, pump knocking |
How do you track down a leak?
Visual inspection
Always start with a visual round of the system. Look for drops, traces of liquid or salt and buffer deposits. White crystal formation on fittings or connections is a reliable sign of an old or intermittent leak that previously went unnoticed.
Soapy water or leak detection fluid
A classic but still very effective method: apply a small amount of soapy liquid or commercial leak detection fluid to the connection to be checked. If the amount of foam increases or bubbles form, there is a leak. This method works particularly well for small leaks that are difficult to see visually.
White paper under the system
Place a sheet of white paper or an absorbent cloth under the system and let the system run at normal operating pressure. Stains on the paper indicate the location of the leak. Combine this with visual inspection to find the exact location.
Use pressure as a detection tool
Temporarily increase the system pressure (within specification) and carry out a visual inspection round. Small leaks that are barely visible at working pressure become more obvious at higher pressure. Only do this if the system safely allows it.
Common mistakes when installing fittings
Most leaks in HPLC systems are caused by installation errors, not by defective components. The most common are listed below:
Tightening too loosely or too tightly
PEEK fittings are tightened by hand and then given an extra quarter turn. Overtightening damages the PEEK material and the instrument port. Tightening too loosely causes leakage. Stainless steel fittings require a wrench and a specific tightening torque; consult the manufacturer's manual.
Incorrect ferrule position
The ferrule must be positioned at the right point on the capillary before it is finally tightened. With stainless steel ferrules, this is an irreversible process: the ferrule sets in the position of the first installation. If it is then placed in a different port, the sealing surface no longer fits and leakage is unavoidable. PEEK ferrules and fingertight fittings can be repositioned.
Wrong capillary for the fitting type
Every fitting is designed for a specific capillary outer diameter. A 10-32 fitting for a 1/16 inch OD capillary does not work correctly with a 1/8 inch OD capillary, even if the fitting appears to fit. Always check that the combination of fitting, ferrule and capillary has the same nominal outer diameter.
Salt deposits as a hidden signal
If you see white crystal formation around a fitting after using buffers or salt solutions, there is almost certainly a small or intermittent leak. Replace the fitting and the ferrule, even if no active leak is visible at that moment. Salt deposits corrode steel fittings and disrupt the measurement.
Preventive maintenance of couplings and fittings
Systematic preventive maintenance extends the life of fittings, reduces unplanned downtime and improves the reproducibility of your analyses. Include the following points in your maintenance programme:
- Visually inspect all connections at every system start-up or after a shutdown of more than a week
- Replace ferrules every time a capillary or fitting in the high-pressure zone is replaced
- Check check valves in the event of unexplained pressure instability or uneven flow
- Do not loosen and retighten fittings in the high-pressure zone unnecessarily: every cycle wears the seal
- Record the installation date of plunger seals and rotor seals and replace them at fixed intervals
- Never use Teflon tape or other sealants on HPLC fittings: this causes dead volume and contamination
